Volume 10, Issue 21, June 12, 2018

CDC Science Clips: Volume 10, Issue 21, June 12, 2018

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreExternal to track social and mainstream media mentions!

  1. Top Articles of the Week

    Selected weekly by a senior CDC scientist from the standard sections listed below.

    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Projected cancer incidence rates and burden of incident cancer cases in HIV-infected adults in the United States through 2030External
        Shiels MS, Islam JY, Rosenberg PS, Hall HI, Jacobson E, Engels EA.
        Ann Intern Med. 2018 May 8.

        Background: Persons living with HIV (PLWH) have an elevated risk for certain types of cancer. With modern antiretroviral therapy, PLWH are aging and cancer rates are changing. Objective: To project cancer incidence rates and burden (number of new cancer diagnoses) among adult PLWH in the United States through 2030. Design: Descriptive. Setting: HIV/AIDS Cancer Match Study to project cancer rates and HIV Optimization and Prevention Economics model to project HIV prevalence. Participants: HIV-infected adults. Measurements: Projected cancer rates and burden among HIV-infected adults in the United States by age during 2006 to 2030 for AIDS-defining cancer (ADC)-that is, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer-and certain types of non-AIDS-defining cancer (NADC). All other cancer types were combined. Results: The proportion of adult PLWH in the United States aged 65 years or older is projected to increase from 8.5% in 2010 to 21.4% in 2030. Age-specific rates are projected to decrease through 2030 across age groups for Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer, lung cancer, Hodgkin lymphoma, and other cancer types combined, and among those aged 65 years or older for colon cancer. Prostate cancer rates are projected to increase. The estimated total cancer burden in PLWH will decrease from 8150 cases in 2010 (2730 of ADC and 5420 of NADC) to 6690 cases in 2030 (720 of ADC and 5980 of NADC). In 2030, prostate cancer (n = 1590) and lung cancer (n = 1030) are projected to be the most common cancer types. Limitation: Projections assume that current trends in cancer incidence rates, HIV transmission, and survival will continue. Conclusion: The cancer burden among PLWH is projected to shift, with prostate and lung cancer expected to emerge as the most common types by 2030. Cancer will remain an important comorbid condition, and expanded access to HIV therapies and cancer prevention, screening, and treatment is needed. Primary Funding Source: National Cancer Institute.

    • Communicable Diseases
      • Expanding hospital human immunodeficiency virus testing in the Bronx, New York and Washington, District of Columbia: Results From the HPTN 065 StudyExternal
        Branson BM, Chavez PR, Hanscom B, Greene E, McKinstry L, Buchacz K, Beauchamp G, Gamble T, Zingman BS, Telzak E, Naab T, Fitzpatrick L, El-Sadr WM.
        Clin Infect Dis. 2018 May 2;66(10):1581-1587.

        Background: Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods: To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results: From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and 13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. Conclusions: Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

    • Drug Safety
      • Trends in prescription medication use among children and adolescents – United States, 1999-2014External
        Hales CM, Kit BK, Gu Q, Ogden CL.
        Jama. 2018 May 15;319(19):2009-2020.

        Importance: Access to appropriate prescription medications, use of inappropriate or ineffective treatments, and adverse drug events are public health concerns among US children and adolescents. Objective: To evaluate trends in use of prescription medications among US children and adolescents. Design, Setting, and Participants: US children and adolescents aged 0 to 19 years in the 1999-2014 National Health and Nutrition Examination Survey (NHANES)-serial cross-sectional, nationally representative surveys of the civilian noninstitutionalized population. Exposures: Sex, age, race and Hispanic origin, household income and education, insurance status, current health status. Main Outcomes and Measures: Use of any prescription medications or 2 or more prescription medications taken in the past 30 days; use of medications by therapeutic class; trends in medication use across 4-year periods from 1999-2002 to 2011-2014. Data were collected though in-home interview and direct observation of the prescription container. Results: Data on prescription medication use were available for 38277 children and adolescents (mean age, 10 years; 49% girls). Overall, use of any prescription medication in the past 30 days decreased from 24.6% (95% CI, 22.6% to 26.6%) in 1999-2002 to 21.9% (95% CI, 20.3% to 23.6%) in 2011-2014 (beta = -0.41 percentage points every 2 years [95% CI, -0.79 to -0.03]; P = .04), but there was no linear trend in the use of 2 or more prescription medications (8.5% [95% CI, 7.6% to 9.4%] in 2011-2014). In 2011-2014, the most commonly used medication classes were asthma medications (6.1% [95% CI, 5.4% to 6.8%]), antibiotics (4.5% [95% CI, 3.7% to 5.5%]), attention-deficit/hyperactivity disorder (ADHD) medications (3.5% [95% CI, 2.9% to 4.2%]), topical agents (eg, dermatologic agents, nasal steroids) (3.5% [95% CI, 3.0% to 4.1%]), and antihistamines (2.0% [95% CI, 1.7% to 2.5%]). There were significant linear trends in 14 of 39 therapeutic classes or subclasses, or in individual medications, with 8 showing increases, including asthma and ADHD medications and contraceptives, and 6 showing decreases, including antibiotics, antihistamines, and upper respiratory combination medications. Conclusions and Relevance: In this study of US children and adolescents based on a nationally representative survey, estimates of prescription medication use showed an overall decrease in use of any medication from 1999-2014. The prevalence of asthma medication, ADHD medication, and contraceptive use increased among certain age groups, whereas use of antibiotics, antihistamines, and upper respiratory combination medications decreased.

    • Food Safety
      • Listeriosis outbreaks associated with soft cheeses, United States, 1998-2014External
        Jackson KA, Gould LH, Hunter JC, Kucerova Z, Jackson B.
        Emerg Infect Dis. 2018 Jun;24(6):1116-1118.

        Since 2006, the number of reported US listeriosis outbreaks associated with cheese made under unsanitary conditions has increased. Two-thirds were linked to Latin-style soft cheese, often affecting pregnant Hispanic women and their newborns. Adherence to pasteurization protocols and sanitation measures to avoid contamination after pasteurization can reduce future outbreaks.

    • Healthcare Associated Infections
      • Regional epidemiology of methicillin-resistant Staphylococcus aureus among adult intensive care unit patients following state-mandated active surveillanceExternal
        Lin MY, Hayden MK, Lyles RD, Lolans K, Fogg LF, Kallen AJ, Weber SG, Weinstein RA, Trick WE.
        Clin Infect Dis. 2018 May 2;66(10):1535-1539.

        Background: In 2007, Illinois became the first state in the United States to mandate active surveillance of methicillin-resistant Staphylococcus aureus (MRSA). The Illinois law applies to intensive care unit (ICU) patients; contact precautions are required for patients found to be MRSA colonized. However, the effectiveness of a legislated “search and isolate” approach to reduce MRSA burden among critically ill patients is uncertain. We evaluated whether the prevalence of MRSA colonization declined in the 5 years after the start of mandatory active surveillance. Methods: All hospitals with an ICU having >/=10 beds in Chicago, Illinois, were eligible to participate in single-day serial point prevalence surveys. We assessed MRSA colonization among adult ICU patients present at time of survey using nasal and inguinal swab cultures. The primary outcome was region-wide MRSA colonization prevalence over time. Results: All 25 eligible hospitals (51 ICUs) participated in serial point prevalence surveys over 8 survey periods (2008-2013). A total of 3909 adult ICU patients participated in the point prevalence surveys, with 432 (11.1%) found to be colonized with MRSA (95% confidence interval [CI], 10.1%-12.0%). The MRSA colonization prevalence among patients was unchanged during the study period; year-over-year relative risk for MRSA colonization was 0.97 (95% CI, .89-1.05; P = .48). Conclusions: MRSA colonization prevalence among critically ill adult patients did not decline during the time period following legislatively mandated MRSA active surveillance. Our findings highlight the limits of legislated MRSA active surveillance as a strategy to reduce MRSA colonization burden among ICU patients.

    • Laboratory Sciences
      • Microcystin (MC) peptides produced by cyanobacteria pose a hepatotoxic threat to human health upon ingestion from contaminated drinking water. While rapid MC identification and quantification in contaminated body fluids or tissue samples is important for patient treatment and outcomes, conventional immunoassay-based measurement strategies typically lack the specificity required for unambiguous determination of specific MC variants, whose toxicity can significantly vary depending on their structures. Furthermore, the unambiguous identification and accurate quantitation of MC variants using tandem mass spectrometry (MS/MS)-based methods can be limited due to a current lack of appropriate stable isotope-labeled internal standards. To address these limitations, we have systematically examined here the sequence and charge state dependence to the formation and absolute abundance of both “global” and “variant-specific” product ions from representative MC-LR, MC-YR, MC-RR, and MC-LA peptides, using higher-energy collisional dissociation (HCD)-MS/MS, ion-trap collision-induced dissociation (CID)-MS/MS and CID-MS(3), and 193 nm ultraviolet photodissociation (UPVD)-MS/MS. HCD-MS/MS was found to provide the greatest detection sensitivity for both global and variant-specific product ions in each of the MC variants, except for MC-YR where a variant-specific product uniquely formed via UPVD-MS/MS was observed with the greatest absolute abundance. A simple methodology for the preparation and characterization of (18)O-stable isotope-labeled MC reference materials for use as internal standards was also developed. Finally, we have demonstrated the applicability of the methods developed herein for absolute quantification of MC-LR present in human urine samples, using capillary scale liquid chromatography coupled with ultra-high resolution / accurate mass spectrometry and HCD-MS/MS. Graphical abstract .

    • Occupational Safety and Health
      • Lead exposure among workers at a shipyard – Wisconsin, 2015-2016External
        Weiss D, Baertlein LA, Yendell SJ, Christensen KY, Tomasallo CD, Creswell PD, Camponeschi JL, Meiman JG, Anderson HA.
        J Occup Environ Med. 2018 May 30.

        OBJECTIVE: In March 2016, the state health departments of Wisconsin and Minnesota learned of three shipyard workers with blood lead levels (BLLs) >40 mug/dL. An investigation was conducted to determine the extent of and risk factors for the exposure. METHODS: We defined a case as an elevated BLL >/=5 mug/dL in a shipyard worker. Workers were interviewed regarding their symptoms and personal protective equipment (PPE) use. RESULTS: Of 357 workers, 65.0% had received >/=1 BLL test. Among tested workers, 171 (73.7%) had BLLmax >/=5 mug/dL. Workers who received respirator training or fit testing had a median BLLmax of 18.0 mug/dL, similar to the median BLLmax of workers who did not receive such training (22.6 mug/dL, P = 0.20). CONCLUSIONS: Our findings emphasize the importance of adequate provision and use of PPE to prevent occupational lead exposure.

    • Physical Activity
      • Proportion of adults who identified walking as a US Surgeon General priorityExternal
        Kumar GS, Watson KB, Brown DR, Carlson SA.
        Prev Chronic Dis. 2018 May 24;15:E62.

        In September 2015, Step It Up! The Surgeon General’s Call to Action to Promote Walking and Walkable Communities (Call to Action) was released. This descriptive study reports the proportion of adults who responded to the 2016 Summer ConsumerStyles survey (N = 4,114) who identified walking as the activity the US Surgeon General recently promoted in the Call to Action to help Americans be more physically active. Less than half of adults (44%) correctly identified walking. Adults who were aged 18 to 24 years (35%), were male (43%), were non-Hispanic white (42%), or were physically inactive (36%) were less likely to identify walking than their counterparts. This study highlights an opportunity to raise awareness and promote the Call to Action, especially among certain populations.

    • Substance Use and Abuse
      • Does state Medicaid coverage of smoking cessation treatments affect quitting?External
        Kostova D, Xu X, Babb S, McMenamin SB, King BA.
        Health Serv Res. 2018 May 27.

        OBJECTIVE: Cigarette smoking and smoking-related diseases disproportionately affect low-income populations. Health insurance coverage of smoking cessation treatments is increasingly used to encourage quitting. We assess the relationship between state Medicaid coverage of smoking cessation treatments and past-year quitting in adult Medicaid beneficiaries. DATA SOURCES: 2009-2014 National Health Interview Survey (NHIS); 2008-2013 indicators of state Medicaid coverage of smoking cessation treatments. STUDY DESIGN: A triple-differencing specification based on differences in Medicaid cessation coverage policies across states as well as within-state differences between Medicaid beneficiaries and a counterfactual group of low-income adults not covered by Medicaid. DATA COLLECTION/EXTRACTION METHODS: Individual-level NHIS data with restricted geographical identifiers were merged with state-year Medicaid coverage indicators. PRINCIPAL FINDINGS: Combined coverage of both cessation counseling and medications in state Medicaid programs was associated with increased quitting, with an estimated mean increase in past-year quitting of 3.0 percentage points in covered Medicaid beneficiaries relative to persons without coverage. CONCLUSIONS: Combined coverage of both smoking cessation counseling and medication by state Medicaid programs could help reduce cigarette smoking among Medicaid beneficiaries.

    • Zoonotic and Vectorborne Diseases
      • Symptomatic Zika virus infection in infants, children, and adolescents living in Puerto RicoExternal
        Read JS, Torres-Velasquez B, Lorenzi O, Rivera Sanchez A, Torres-Torres S, Rivera LV, Capre-Franceschi SM, Garcia-Gubern C, Munoz-Jordan J, Santiago GA, Alvarado LI.
        JAMA Pediatr. 2018 May 29.

        Importance: Little information is available regarding Zika virus (ZIKV) infection in children. Objective: To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS). Design, Setting, and Participants: Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 to 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before December 31, 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction-positive specimens were evaluated to determine viral loads. Exposures: Confirmed polymerase chain reaction-positive ZIKV infection. Main Outcomes and Measures: Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection. Results: Of 7191 children enrolled in SEDSS on or before December 31, 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1%), 69 children (19.7%) aged 1 to 4 years, 95 (27.1%) aged 5 to 9 years, and 162 (46.1%) aged 10 to 17 years. Among these, 260 patients (74.1%) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9%) were discharged to home after evaluation, and 349 (99.4%) had fever, 280 (79.8%) had a rash, 243 (69.2%) had facial or neck erythema, 234 (66.7%) had fatigue, 223 (63.5%) had headache, 212 (60.4%) had chills, 206 (58.7%) had pruritus, and 204 (58.1%) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23098 [8784-88242] copies/mL for serum vs 9966 [2815-52774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106778 [IQR, 9772-1571718] copies/mL; 1 day, 46299 [10663-255030] copies/mL; 2 days, 20678 [8763-42458] copies/mL; and >/=3 days, 15901 [5135-49248] copies/mL; P = .001). Conclusions and Relevance: This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the onset of symptoms. Viral loads for ZIKV were higher in serum vs urine specimens. Median viral loads in serum specimens differed significantly according to the number of days after the onset of symptoms.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Use of outpatient rehabilitation among adult stroke survivors – 20 states and the District of Columbia, 2013, and four states, 2015External
        Ayala C, Fang J, Luncheon C, King SC, Chang T, Ritchey M, Loustalot F.
        MMWR Morb Mortal Wkly Rep. 2018 May 25;67(20):575-578.

        Stroke is a leading cause of mortality and disability in the United States (1,2). Approximately 800,000 American adults experience a stroke each year (2,3). Currently, approximately 6 million stroke survivors live in the United States (2). Participation in stroke rehabilitation (rehab), which occurs in diverse settings (i.e., in-hospital, postacute care, and outpatient settings), has been determined to reduce stroke recurrence and improve functional outcomes and quality of life (3,4). Despite longstanding national guidelines recommending stroke rehab, it remains underutilized, especially in the outpatient setting. Professional associations and evidence-based guidelines support the increasing stroke rehab use in health systems and are promoted by the public health community (3-6). An analysis of 2005 Behavioral Risk Factor Surveillance System (BRFSS) data revealed that 30.7% of stroke survivors reported participation in outpatient rehab for stroke after hospital discharge in 21 states and the District of Columbia (DC) (7). To update these estimates, 2013 and 2015 BRFSS data were analyzed to assess outpatient rehab use among adult stroke survivors. Overall, outpatient rehab use was 31.2% (20 states and DC) in 2013 and 35.5% (four states) in 2015. Disparities were evident by sex, race, Hispanic origin, and level of education. Focused attention on system-level interventions that ensure participation is needed, especially among disparate populations with lower levels of participation.

      2. A robust evidence base supports the effectiveness of timely colorectal cancer (CRC) screening, follow-up of abnormal results, and referral to care in reducing CRC morbidity and mortality. However, only two-thirds of the US population is current with recommended screening, and rates are much lower for those who are vulnerable because of their race/ethnicity, insurance status, or rural location. Multiple, multilevel factors contribute to observed disparities, and these factors vary across different populations and contexts. As highlighted by the Cancer Moonshot Blue Ribbon Panel working groups focused on Prevention and Early Detection and Implementation Science inadequate CRC screening and follow-up represent an enormous missed opportunity in cancer prevention and control. To measurably reduce CRC morbidity and mortality, the evidence base must be strengthened to guide the identification of (1) multilevel factors that influence screening across different populations and contexts, (2) multilevel interventions and implementation strategies that will be most effective at targeting those factors, and (3) combinations of strategies that interact synergistically to improve outcomes. Systems thinking and simulation modeling (systems science) provide a set of approaches and techniques to aid decision makers in using the best available data and research evidence to guide implementation planning in the context of such complexity. This commentary summarizes current challenges in CRC prevention and control, discusses the status of the evidence base to guide the selection and implementation of multilevel CRC screening interventions, and describes a multi-institution project to showcase how systems science can be leveraged to optimize selection and implementation of CRC screening interventions in diverse populations and contexts.

    • Communicable Diseases
      1. Tuberculosis in the circumpolar region, 2006-2012External
        Bourgeois AC, Zulz T, Bruce MG, Stenz F, Koch A, Parkinson A, Hennessy T, Cooper M, Newberry C, Randell E, Proulx JF, Hanley BE, Soini H, Arnesen TM, Mariandyshev A, Jonsson J, Soborg B, Wolfe J, Balancev G, De Neergaard RB, Archibald CP.
        Int J Tuberc Lung Dis. 2018 ;22(6):641-648.

        Setting: The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). Objective : To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. Design: Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates. Results : The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions. Conclusion: TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north.

      2. First United States outbreak of Mycobacterium abscessus hand and foot disease among children associated with a wading poolExternal
        Carter KK, Lundgren I, Correll S, Schmalz T, McCarter T, Stroud J, Bruesch A, Hahn CG.
        J Pediatric Infect Dis Soc. 2018 May 29.

        Background: Mycobacterium abscessus, an emerging pathogen in healthcare settings, has rarely been associated with community outbreaks. During February-May 2013, Idaho public health officials and pediatric infectious disease physicians investigated an outbreak of M abscessus skin infections in children whose only common exposure was an indoor wading pool. Methods: Healthcare providers and parents reported possible M abscessus cases. We used a standardized questionnaire to interview parents of affected children. Clinical specimens were submitted for mycobacterial examination. We conducted an environmental investigation of the pool. Microbial isolates from clinical and environmental samples were identified by sequencing polymerase chain reaction amplicons and underwent pulsed-field gel electrophoresis. Results: Twelve cases were identified. Specimens from 4 of 7 children grew M abscessus or Mycobacterium abscessus/Mycobacterium chelonae . Ten (83%) of 12 children were female; median age was 3 years (range, 2 to 6 years); and all were immunocompetent. Pool maintenance did not fully comply with Idaho state rules governing pool operation. Mycobacterium abscessus/chelonae was isolated from pool equipment. Pulsed-field gel electrophoresis composite patterns were 87% similar between isolates from the pool ladder and 1 patient, and they were 90% similar between isolates from 2 patients. Environmental remediation included hyperchlorination, scrubbing and disinfection of pool surfaces, draining the pool, and replacement of worn pool materials. Conclusions: Immunocompetent children acquired M abscessus cutaneous infection involving hands and feet after exposure to a wading pool. Environmental remediation and proper pool maintenance likely halted transmission. Medical and public health professionals’ collaboration effectively detected and controlled an outbreak caused by an emerging recreational waterborne pathogen.

      3. Monitoring the hepatitis C care cascade using administrative claims dataExternal
        Isenhour C, Hariri S, Vellozzi C.
        Am J Manag Care. 2018 May;24(5):232-238.

        OBJECTIVES: With the availability of curative therapies, it is important to ensure that individuals infected with hepatitis C virus (HCV) receive recommended testing, care, and treatment. We sought to evaluate insurance claims data as a source for monitoring progression along the HCV care cascade. STUDY DESIGN: Longitudinal evaluation of disease progression, from diagnosis to treatment, among commercially insured enrollees with chronic HCV. METHODS: We validated and used algorithms derived from standardized procedure and diagnosis codes to identify enrollees with chronic HCV in large insurance claims databases to describe the HCV care cascade, including the proportion engaged in HCV-specific care (13 possible definitions), the proportion prescribed HCV treatment, and the proportion who received an HCV RNA test 30 or more days after initiating treatment. RESULTS: Approximately 90% of individuals with an HCV RNA test procedure code followed by either 3 or more chronic HCV diagnosis codes on different service dates or 2 or more chronic HCV diagnosis codes separated by more than 60 days truly had chronic HCV. Using these algorithms, we identified 5791 HCV cases from January 1, 2013, to June 30, 2014. Among enrollees with HCV, 95% were engaged in HCV care, but only 49% initiated treatment and 43% received a follow-up HCV RNA test 30 or more days after initiating treatment. CONCLUSIONS: With validated case-finding algorithms, insurance claims data can be used to describe and monitor portions of the HCV care cascade. Although nearly all enrollees with HCV were engaged in HCV care, only half received treatment, indicating that even commercially insured enrollees may find it challenging to access treatment.

      4. OBJECTIVE: Few studies have examined condom effectiveness for HIV prevention among men who have sex with men (MSM). We estimated condom effectiveness per partner in four cohorts of MSM during 1993-2003 (JumpStart, Vaccine Preparedness Study, VAX004 and Project Explore). METHODS: We used logistic regression to estimate the increase in odds of new HIV infection per HIV-positive partner for condom-protected receptive anal intercourse (PRAI; partners with whom condoms were always used) and condomless (unprotected) receptive anal intercourse (URAI; partners with whom condoms were sometimes or never used). To estimate condom effectiveness for preventing HIV transmission we applied the concept of excess odds, the odds ratio minus 1. The condom failure rate was estimated as the excess odds per PRAI partner divided by the excess odds per URAI partner. Condom effectiveness was then 1 minus the failure rate. RESULTS: The excess odds of HIV infection per HIV-positive partner were 83% for URAI and 7% for PRAI. The resulting failure rate (9%) indicated per-partner condom effectiveness of 91% (95% confidence interval 69-101). CONCLUSION: The increase in odds of new HIV infection per HIV-positive partner for RAI was reduced by 91% for each partner with whom condoms were always used.

      5. Progress toward rubella and congenital rubella syndrome control – South-East Asia Region, 2000-2016External
        Khanal S, Bahl S, Sharifuzzaman M, Dhongde D, Pattamadilok S, Reef S, Morales M, Dabbagh A, Kretsinger K, Patel M.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 1;67(21):602-606.

        In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control(dagger) of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of >/=95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed.

      6. Prevalence and correlates of non-disclosure of maternal HIV status to male partners: a national survey in KenyaExternal
        Kinuthia J, Singa B, McGrath CJ, Odeny B, Langat A, Katana A, Ng’ang’a L, Pintye J, John-Stewart G.
        BMC Public Health. 2018 May 30;18(1):671.

        BACKGROUND: Prevention of mother-to-child HIV transmission (PMTCT) programs usually test pregnant women for HIV without involving their partners. Non-disclosure of maternal HIV status to male partners may deter utilization of PMTCT interventions since partners play a pivotal role in decision-making within the home including access to and utilization of health services. METHODS: Mothers attending routine 6-week and 9-month infant immunizations were enrolled at 141 maternal and child health (MCH) clinics across Kenya from June-December 2013. The current analysis was restricted to mothers with known HIV status who had a current partner. Multivariate logistic regression models adjusted for marital status, relationship length and partner attendance at antenatal care (ANC) were used to determine correlates of HIV non-disclosure among HIV-uninfected and HIV-infected mothers, separately, and to evaluate the relationship of non-disclosure with uptake of PMTCT interventions. All analyses accounted for facility-level clustering, RESULTS: Overall, 2522 mothers (86% of total study population) met inclusion criteria, 420 (17%) were HIV-infected. Non-disclosure of HIV results to partners was higher among HIV-infected than HIV-uninfected women (13% versus 3% respectively, p < 0.001). HIV-uninfected mothers were more likely to not disclose their HIV status to male partners if they were unmarried (adjusted odds ratio [aOR] = 3.79, 95% CI: 1.56-9.19, p = 0.004), had low (</=KSH 5000) income (aOR = 1.85, 95% CI: 1.00-3.14, p = 0.050), experienced intimate partner violence (aOR = 3.65, 95% CI: 1.84-7.21, p < 0.001) and if their partner did not attend ANC (aOR = 4.12, 95% CI: 1.89-8.95, p < 0.001). Among HIV-infected women, non-disclosure to male partners was less likely if women had salaried employment (aOR = 0.42, 95%CI: 0.18-0.96, p = 0.039) and each increasing year of relationship length was associated with decreased likelihood of non-disclosure (aOR = 0.90, 95% CI: 0.82-0.98, p = 0.015 for each year increase). HIV-infected women who did not disclose their HIV status to partners were less likely to uptake CD4 testing (aOR = 0.32, 95% CI: 0.15-0.69, p = 0.004), to use antiretrovirals (ARVs) during labor (OR = 0.38, 95% CI 0.15-0.97, p = 0.042), or give their infants ARVs (OR = 0.08, 95% CI 0.02-0.31, p < 0.001). CONCLUSION: HIV-infected women were less likely to disclose their status to partners than HIV-uninfected women. Non-disclosure was associated with lower use of PMTCT services. Facilitating maternal disclosure to male partners may enhance PMTCT uptake.

      7. Optimizing community-based HIV testing and linkage to care for young persons in metropolitan AtlantaExternal
        Murray A, Hussen SA, Toledo L, Thomas-Seaton L, Gillespie S, Graves C, Chakraborty R, Sutton MY, Camacho-Gonzalez AF.
        AIDS Patient Care STDS. 2018 Jun;32(6):234-240.

        HIV continuum of care analyses in Georgia during 2013 revealed that 82% of adolescents and adults living with HIV knew their diagnosis and that 75% were linked to care. However, of all persons in Georgia living with HIV in 2014, only 60% had at least one HIV care visit, and just 48% were retained in care. Understanding barriers for HIV testing, linkage, and retention in youth may strengthen HIV-related encounters and improve patient outcomes. We conducted 17 qualitative focus groups with HIV-positive and -negative youth, ages 18-24 years, from the Atlanta Metropolitan Statistical Area. Using computer-assisted thematic analyses, we examined focus group responses on ways to approach youth for community-based HIV testing and how service providers should discuss a new positive HIV diagnosis with youth. Of 68 participants, 85% were male, 90% were African American, 68% were HIV positive, and 50% had high school education or less. Mean age was 21.5 years (standard deviation: 1.8 years). Thematic analyses identified the following three key themes for approaching someone for HIV testing: (1) discretion, (2) being candid about testing, and (3) incentivizing testing. When service providers discuss an HIV positive test, participants recommended enhanced emotional support and reassurance of a potential healthy life span despite an HIV diagnosis. Community-based testing may be a viable option for increasing HIV screening of at-risk youth. Structuring an empathetic new diagnosis disclosure that addresses potential misconceptions and describes successful HIV treatment is essential to improving linkage to care among youth.

      8. TB preventive therapy for people living with HIV: Key considerations for scale-up in resource-limited settingsExternal
        Pathmanathan I, Ahmedov S, Pevzner E, Anyalechi G, Modi S, Kirking H, Cavanaugh JS.
        Int J Tuberc Lung Dis. 2018 ;22(6):596-605.

        Tuberculosis (TB) is the leading cause of death for persons living with the human immunodeficiency virus (PLHIV). TB preventive therapy (TPT) works synergistically with, and independently of, antiretroviral therapy to reduce TB morbidity, mortality and incidence among PLHIV. However, although TPT is a crucial and costeffective component of HIV care for adults and children and has been recommended as an international standard of care for over a decade, it remains highly underutilized. If we are to end the global TB epidemic, we must address the significant reservoir of tuberculous infection, especially in those, such as PLHIV, who are most likely to progress to TB disease. To do so, we must confront the pervasive perception that barriers to TPT scale-up are insurmountable in resource-limited settings. Here we review available evidence to address several commonly stated obstacles to TPT scale-up, including the need for the tuberculin skin test, limited diagnostic capacity to reliably exclude TB disease, concerns about creating drug resistance, suboptimal patient adherence to therapy, inability to monitor for and prevent adverse events, a ‘one size fits all’ option for TPT regimen and duration, and uncertainty about TPT use in children, adolescents, and pregnant women. We also discuss TPT delivery in the era of differentiated care for PLHIV, how best to tackle advanced planning for drug procurement and supply chain management, and how to create an enabling environment for TPT scale-up success.

      9. Severe respiratory illness associated with rhinovirus during the enterovirus D68 outbreak in the United States, August 2014-November 2014External
        Prill MM, Dahl RM, Midgley CM, Chern SW, Lu X, Feikin DR, Sakthivel SK, Nix WA, Watson JT, Gerber SI, Oberste MS.
        Clin Infect Dis. 2018 May 2;66(10):1528-1534.

        Background: In 2014, a nationwide outbreak of severe respiratory illness occurred in the United States, primarily associated with enterovirus D68 (EV-D68). A proportion of illness was associated with rhinoviruses (RVs) and other enteroviruses (EVs), which we aimed to characterize further. Methods: Respiratory specimens from pediatric and adult patients with respiratory illness were submitted to the Centers for Disease Control and Prevention during August 2014-November 2014. While initial laboratory testing focused on identification of EV-D68, the negative specimens were typed by molecular sequencing to identify additional EV and RV types. Testing for other pathogens was not conducted. We compared available clinical and epidemiologic characteristics among patients with EV-D68 and RV species A-C identified. Results: Among 2629 typed specimens, 1012 were EV-D68 (39%) and 81 (3.1%) represented 24 other EV types; 968 were RVs (37%) covering 114 types and grouped into 3 human RV species (RV-A, 446; RV-B, 133; RV-C, 389); and 568 (22%) had no RV or EV detected. EV-D68 was more frequently identified in patients who presented earlier in the investigation period. Among patients with EV-D68, RV-A, RV-B, or RV-C, the age distributions markedly differed. Clinical syndromes and intensive care unit admissions by age were largely similar. Conclusions: RVs were commonly associated with severe respiratory illness during a nationwide outbreak of EV-D68, and most clinical. Characteristics were similar between groups. A better understanding of the epidemiology of RVs and EVs is needed to help inform development and use of diagnostic tests, therapeutics, and preventive measures.

      10. Respiratory syncytial virus hospitalization during pregnancy in four high-income countries, 2010-2016External
        Regan AK, Klein NP, Langley G, Drews SJ, Buchan S, Ball S, Kwong JC, Naleway A, Thompson M, Wyant BE, Levy A, Chung H, Feldman B, Katz M.
        Clin Infect Dis. 2018 May 24.

        [No abstract]

      11. Assessing disparities in the rates of HCV diagnoses within American Indian or Alaska Native populations served by the U.S. Indian Health Service, 2005-2015External
        Reilley B, Leston J, Doshani M, Haberling DL, Person M, Weiser T, Collier M, Iralu J, Mera J, Haverkate R.
        J Community Health. 2018 May 28.

        Hepatitis C virus (HCV) disproportionately affects American Indians/Alaska Natives (AI/AN). The Indian Health Service (IHS), via federal and tribal health facilities provides medical services to an estimated 2.2 million AI/AN people in the United States. HCV diagnoses, defined by International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM) codes, were analyzed from 2005 to 2015. Results showed 29,803 patients with an HCV diagnosis; 53.4% were among persons born 1945-1965 and overall HCV burden was higher among males than females. These data will help inform local, regional, and national efforts to address, plan for and carry out a national strategy to provide treatment for HCV infected patients and programs to prevent new HCV infections.

      12. An update from hospital-based surveillance for rotavirus gastroenteritis among young children in Bangladesh, July 2012 to June 2017External
        Satter SM, Aliabadi N, Gastanaduy PA, Haque W, Mamun A, Flora MS, Zaman K, Rahman M, Heffelfinger JD, Luby SP, Gurley ES, Parashar UD.
        Vaccine. 2018 May 21.

        INTRODUCTION: In preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. METHODS: We enrolled and collected fresh stool from every fourth child<5years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. RESULTS: We found that 64% (4832/7562) of children<5years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were <12months of age. The most common strains were G1P[8] (43%), G12P[8] (15%) and G9P[8] (9%); 11% of children had mixed infection.G3P[8], which has not been reported in Bangladesh since 2001, was documented for the first time in our surveillance system. CONCLUSIONS: The high burden of rotavirus-associated hospitalizations highlights the potential value of rotavirus vaccination in Bangladesh. Continued surveillance is important for monitoring the impact of vaccination as well as monitoring evolving genotypes.

      13. BACKGROUND: Factors that affect latent tuberculosis infection (LTBI) treatment completion in the US have not been well studied beyond public health settings. This gap was highlighted by recent health insurance-related regulatory changes that are likely to increase LTBI treatment by private sector healthcare providers. We analyzed LTBI treatment completion in the private healthcare setting to facilitate planning around this important opportunity for tuberculosis (TB) control in the US. METHODS: We analyzed a national sample of commercial insurance medical and pharmacy claims data for people ages 0 to 64 years who initiated daily dose isoniazid treatment between July 2011 and March 2014 and who had complete data. All individuals resided in the US. Factors associated with treatment completion were examined using multivariable generalized ordered logit models and bivariate Kruskal-Wallis tests or Spearman correlations. RESULTS: We identified 1072 individuals with complete data who initiated isoniazid LTBI treatment. Treatment completion was significantly associated with less restrictive health insurance, age < 15 years, patient location, use of interferon-gamma release assays, non-poverty, HIV diagnosis, immunosuppressive drug therapy, and higher cumulative counts of clinical risk factors. CONCLUSIONS: Private sector healthcare claims data provide insights into LTBI treatment completion patterns and patient/provider behaviors. Such information is critical to understanding the opportunities and limitations of private healthcare in the US to support treatment completion as this sector’s role in protecting against and eliminating TB grows.

      14. Seasonal incidence of symptomatic influenza in the United StatesExternal
        Tokars JI, Olsen SJ, Reed C.
        Clin Infect Dis. 2018 May 2;66(10):1511-1518.

        Background: The seasonal incidence of influenza is often approximated as 5%-20%. Methods: We used 2 methods to estimate the seasonal incidence of symptomatic influenza in the United States. First, we made a statistical estimate extrapolated from influenza-associated hospitalization rates for 2010-2011 to 2015-2016, collected as part of national surveillance, covering approximately 9% of the United States, and including the existing mix of vaccinated and unvaccinated persons. Second, we performed a literature search and meta-analysis of published manuscripts that followed cohorts of subjects during 1996-2016 to detect laboratory-confirmed symptomatic influenza among unvaccinated persons; we adjusted this result to the US median vaccination coverage and effectiveness during 2010-2016. Results: The statistical estimate of influenza incidence among all ages ranged from 3.0%-11.3% among seasons, with median values of 8.3% (95% confidence interval [CI], 7.3%-9.7%) for all ages, 9.3% (95% CI, 8.2%-11.1%) for children <18 years, and 8.9% (95% CI, 8.2%-9.9%) for adults 18-64 years. Corresponding values for the meta-analysis were 7.1% (95% CI, 6.1%-8.1%) for all ages, 8.7% (95% CI, 6.6%-10.5%) for children, and 5.1% (95% CI, 3.6%-6.6%) for adults. Conclusions: The 2 approaches produced comparable results for children and persons of all ages. The statistical estimates are more versatile and permit estimation of season-to-season variation. During 2010-2016, the incidence of symptomatic influenza among vaccinated and unvaccinated US residents, including both medically attended and nonattended infections, was approximately 8% and varied from 3% to 11% among seasons.

      15. Intra-host and intra-household diversity of influenza A viruses during household transmissions in the 2013 season in 2 peri-urban communities of South AfricaExternal
        Valley-Omar Z, Iyengar P, von Mollendorf C, Tempia S, Moerdyk A, Hellferscee O, Martinson N, McMorrow M, Variava E, Masonoke K, Cohen AL, Cohen C, Treurnicht FK.
        PLoS One. 2018 ;13(5):e0198101.

        Limited information is available on influenza virus sequence drift between transmission events. In countries with high HIV burdens, like South Africa, the direct and indirect effect of HIV on influenza sequence drift between transmission events may be of public health concern. To this end, we measured hemagglutinin sequence diversity between influenza transmission events using data and specimens from a study investigating household transmission dynamics of seasonal influenza viruses in 2 peri-urban communities in South Africa during the 2013 influenza season. Thirty index cases and 107 of 110 eligible household contacts were enrolled into the study, 47% (14/30) demonstrating intra-household laboratory-confirmed influenza transmission. In this study 35 partial hemagglutinin gene sequences were obtained by Sanger sequencing from 11 index cases (sampled at enrolment only) and 16 secondary cases (8 cases sampled at 1 and 8 cases sampled at 2 time-points). Viral sequence identities confirmed matched influenza transmission pairs within the 11 households with corresponding sequenced index and secondary cases. Phylogenetic analysis revealed 10 different influenza viral lineages in the 14 households. Influenza A(H1N1)pdm09 strains were shown to be genetically distinct between the 2 communities (from distinct geographic regions), which was not observed for the influenza A(H3N2) strains. Intra-host/intra-household influenza A(H3N2) sequence drift was identified in 2 households. The first was a synonymous mutation between the index case and a household contact, and the second a non-synonymous mutation between 2 serial samples taken at days 0 and 4 post enrolment from an HIV-infected secondary case. Limited inter-household sequence diversity was observed as highlighted by sharing of the same influenza strain between different households within each community. The limited intra-household sequence drift is in line with previous studies also using Sanger sequencing, corroborating the presence of strict selective bottlenecks that limit sequence variance. We were not able to directly ascertain the effect of HIV on influenza sequence drift between transmission events.

      16. Influenza viral shedding in a prospective cohort of HIV-infected and -uninfected children and adults in 2 provinces of South Africa, 2012-2014External
        von Mollendorf C, Hellferscee O, Valley-Omar Z, Treurnicht FK, Walaza S, Martinson NA, Lebina L, Mothlaoleng K, Mahlase G, Variava E, Cohen AL, Venter M, Cohen C, Tempia S.
        J Infect Dis. 2018 May 24.

        Background: Prolonged shedding of influenza viruses may be associated with increased transmissibility and resistance mutation acquisition due to therapy. We compared duration and magnitude of influenza shedding between HIV-infected and -uninfected individuals. Methods: A prospective cohort study during three influenza seasons enrolled patients with influenza-like illness and a positive influenza rapid test. Influenza viruses were detected by real-time reverse transcription polymerase chain reaction. Weibull accelerated failure time regression models were used to describe influenza virus shedding. Mann-Whitney U tests explored initial influenza viral loads (VL). Results: Influenza virus shedding duration was similar in 65 HIV-infected (6 [interquartile range (IQR) 3-10] days) and 176 HIV-uninfected individuals (7 [IQR 4-11] days, p=0.97), as was initial influenza VL (HIV-uninfected 5.28 +/- 1.33 log10 copies/mL, HIV-infected 4.73 +/- 1.68 log10 copies/mL, p=0.08). Adjusted for age, HIV-infected individuals with low CD4 counts shed influenza virus for longer than those with higher counts (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 1.05-12.08). Discussion: A longer duration of influenza virus shedding in HIV-infected individuals with low CD4 counts may suggest a possible increased risk for transmission or viral evolution in severely immunocompromised individuals. HIV-infected individuals should be prioritized for annual influenza immunization.

    • Disease Reservoirs and Vectors
      1. Rickettsia parkeri in Dermacentor parumapertus Ticks, MexicoExternal
        Sanchez-Montes S, Lopez-Perez AM, Guzman-Cornejo C, Colunga-Salas P, Becker I, Delgado-de la Mora J, Licona-Enriquez JD, Delgado-de la Mora D, Karpathy SE, Paddock CD, Suzan G.
        Emerg Infect Dis. 2018 Jun;24(6):1108-1111.

        During a study to identify zoonotic pathogens in northwestern Mexico, we detected the presence of a rickettsial agent in Dermacentor parumapertus ticks from black-tailed jackrabbits (Lepus californicus). Comparison of 4 gene sequences (gltA, htrA, ompA, and ompB) of this agent showed 99%-100% identity with sequences of Rickettsia parkeri.

    • Drug Safety
      1. Impact of an antimicrobial stewardship program on outcomes in patients with community-acquired pneumonia admitted to a tertiary community hospitalExternal
        Gordon K, Stevens R, Westley B, Bulkow L.
        Am J Health Syst Pharm. 2018 Jun 1;75(11 Supplement 2):S42-s50.

        PURPOSE: Results of a study evaluating the impact of an antimicrobial stewardship program (ASP) on clinical outcomes in patients hospitalized for community-acquired pneumonia (CAP) are reported. METHODS: A retrospective records review was conducted at a 400-bed hospital to identify patients admitted over 3 years with CAP documented as a primary or secondary diagnosis. Clinical and medication-use outcomes during a 1-year baseline period and in the first and second years after ASP implementation (post-ASP years 1 and 2) were analyzed. A local CAP guideline was implemented around the beginning of post-ASP year 2. RESULTS: The mean hospital length of stay declined from 7.24 days in the baseline period to 5.71 days in post-ASP year 1 (p = 0.011) and 5.52 days in post-ASP year 2 (p = 0.008). Mean inpatient antimicrobial days of therapy (DOT) declined from 5.68 days in the baseline period to 5.08 days (p = 0.045) and 4.99 days (p = 0.030) in post-ASP years 1 and 2, respectively. Mean DOT per 100 total days of antimicrobial therapy declined from 9.69 days in the baseline period to 8.85 days in post-ASP year 1 (p = 0.019) and 8.38 days in post-ASP year 2 (p = 0.001). CONCLUSION: ASP implementation was associated with specific clinical benefits in patients with CAP, including decreased length of stay, decreased durations of antimicrobial therapy, and a shift in utilization to a primary regimen shown to produce superior clinical outcomes.

    • Environmental Health
      1. Associations of maternal exposure to triclosan, parabens, and other phenols with prenatal maternal and neonatal thyroid hormone levelsExternal
        Berger K, Gunier RB, Chevrier J, Calafat AM, Ye X, Eskenazi B, Harley KG.
        Environ Res. 2018 May 24;165:379-386.

        Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N=454) and TSH in their neonates (N=365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (beta for two-fold increase = -3.26%, 95% CI: -5.55, -0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (beta for two-fold increase = -0.05, 95% CI: -0.08, -0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (beta for two-fold increase = -0.05, 95% CI: -0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.

    • Epidemiology and Surveillance
      1. Systematic assessment of multiple routine and near real-time indicators to classify the severity of influenza seasons and pandemics in the United States, 2003-2004 through 2015-2016External
        Biggerstaff M, Kniss K, Jernigan DB, Brammer L, Bresee J, Garg S, Burns E, Reed C.
        Am J Epidemiol. 2018 May 1;187(5):1040-1050.

        Assessments of influenza season severity can guide public health action. We used the moving epidemic method to develop intensity thresholds (ITs) for 3 US surveillance indicators from the 2003-2004 through 2014-2015 influenza seasons (excluding the 2009 pandemic). The indicators were: 1) outpatient visits for influenza-like illness; 2) influenza-related hospitalizations; and 3) influenza- and pneumonia-related deaths. ITs were developed for the population overall and separately for children, adults, and older adults, and they were set at the upper limit of the 50% (IT50), 90% (IT90), and 98% (IT98) 1-sided confidence intervals of the geometric mean of each season’s 3 highest values. Severity was classified as low if >/=2 systems peaked below IT50, moderate if >/=2 peaked between IT50 and IT90, high if >/=2 peaked between IT90 and IT98, and very high if >/=2 peaked above IT98. We pilot-tested this method with the 2015-2016 season and the 2009 pandemic. Overall, 4 seasons were classified as low severity, 7 as moderate, 2 as high, and none as very high. Among the age groups, older adults had the most seasons (n = 3) classified as high, and children were the only group to have seasons (n = 2) classified as very high. We will apply this method to classify the severity of future seasons and inform pandemic response.

    • Food Safety
      1. Saxitoxin exposure confirmed by human urine and food analysisExternal
        Coleman RM, Ojeda-Torres G, Bragg W, Fearey D, McKinney P, Castrodale L, Verbrugge D, Stryker K, DeHart E, Cooper M, Hamelin E, Thomas J, Johnson RC.
        J Anal Toxicol. 2018 May 25.

        A case of an elderly female with suspected paralytic shellfish poisoning (PSP) is presented. The patient shared a meal of recreationally-harvested shellfish with her family and soon began to experience nausea and weakness. She was taken to the local emergency department and then transported to a larger hospital in Anchorage where she was admitted to the intensive care unit with respiratory depression and shock. Her condition improved, and she was discharged from the hospital 6 days later. No others who shared the meal reported symptoms of PSP. A clam remaining from the meal was collected and analyzed for paralytic shellfish toxins (PST) by the Alaska Department of Environmental Conservation Environmental Health Laboratory; the clam tested positive for saxitoxin (STX; 277 mug/100 g), neosaxitoxin (NEO; 309 mug/100 g), multiple gonyautoxins (GTX; 576-2490 mug/100 g), decarbamoyl congeners (7.52-11.3 mug/100 g) and C-toxins (10.8-221 mug/100 g) using high-pressure liquid chromatography with post-column oxidation (AOAC Method 2011.02). Urine from the patient was submitted to Centers for Disease Control for analysis of selected PSTs and creatinine. STX (64.0 mug/g-creatinine), NEO (60.0 mug/g-creatinine) and GTX1-4 (492-4780 mug/g-creatinine) were identified in the urine using online solid phase extraction with HPLC and tandem mass spectrometry. This was the first time GTX were identified in urine of a PSP case from Alaska, highlighting the need to include all STX congeners in testing to protect the public’s health through a better understand of PST toxicity, monitoring and prevention of exposures.

      2. Notes from the field: Cyclosporiasis cases associated with dining at a Mediterranean-style restaurant chain – Texas, 2017External
        Keaton AA, Hall NB, Chancey RJ, Heines V, Cantu V, Vakil V, Long S, Short K, Franciscus E, Wahab N, Haynie A, Gieraltowski L, Straily A.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 1;67(21):609-610.

        [No abstract]

    • Health Economics
      1. Health insurance coverage by occupation among adults aged 18-64 years – 17 states, 2013-2014External
        Boal WL, Li J, Sussell A.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 1;67(21):593-598.

        Lack of health insurance has been associated with poorer health status and with difficulties accessing preventive health services and obtaining medical care, especially for chronic diseases (1-3). Among workers, the prevalence of chronic conditions, risk behaviors, and having health insurance has been shown to vary by occupation (4,5). CDC used data from the 2013 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) to estimate the prevalence of having no health care coverage (e.g., health insurance, prepaid plans such as health maintenance organizations, government plans such as Medicare, or Indian Health Service) by occupation. Among all workers aged 18-64 years, the prevalence of being uninsured declined significantly (21%) from 16.0% in 2013 to 12.7% in 2014. In both years there were large differences in the prevalence of being uninsured among occupational groups, ranging from 3.6% among the architecture and engineering occupations to 37.9% among the farming, fishing, and forestry occupations in 2013 and 2.7% among community and social services; and education, training, and library occupations to 37.0% among building and grounds cleaning and maintenance occupations in 2014 (p<0.001). In 2014, more than 25% of workers in four occupational groups reported having no health insurance (construction and extraction [29.1%]; farming, fishing, and forestry [34.6%]; food preparation and serving related [35.5%]; and building and grounds cleaning and maintenance [37.0%]). Identifying factors affecting differences in coverage by occupation might help to address health disparities among occupational groups.

    • Healthcare Associated Infections
      1. Combatting sepsis: A public health perspectiveExternal
        Dantes RB, Epstein L.
        Clin Infect Dis. 2018 May 29.

        Public health professionals and organizations have an opportunity to create a more comprehensive sepsis prevention strategy that spans the continuum of care and merges existing infection prevention strategies with chronic disease management and improved education on the signs and symptoms of worsening infection and sepsis. Recent public health efforts have improved our understanding of US national sepsis epidemiology and focused on increasing sepsis awareness. Additional opportunities and challenges include creating more integrated sepsis and infection prevention programs that encompass outpatient and inpatient care.

      2. [No abstract]

      3. [No abstract]

      4. Assessment of risk for transplant-transmissible infectious encephalitis among deceased organ donorsExternal
        Smalley HK, Anand N, Buczek D, Buczek N, Lin T, Rajore T, Wacker M, Basavaraju SV, Gurbaxani BM, Hammett T, Keskinocak P, Sokol J, Kuehnert MJ.
        Transpl Infect Dis. 2018 May 29:e12933.

        BACKGROUND: There were 13 documented clusters of infectious encephalitis transmission via organ transplant from deceased donors to recipients during 2002-2013. Hence, organs from donors diagnosed with encephalitis are often declined due to concerns about the possibility of infection, given that there is no quick and simple test to detect causes of infectious encephalitis. METHODS: We constructed a database containing cases of infectious and non-infectious encephalitis. Using statistical imputation, cross-validation, and regression techniques, we determined deceased organ donor characteristics, including demographics, signs, symptoms, physical exam, and laboratory findings, predictive of infectious versus non-infectious encephalitis, and developed a calculator which assesses risk of infection. RESULTS: Using up to 12 predictive patient characteristics, (with a minimum of 3, depending on what information is available), the calculator provides the probability that a donor may have infectious versus non-infectious encephalitis, improving the prediction accuracy over current practices. These characteristics include gender, fever, immunocompromised state (other than HIV), cerebrospinal fluid elevation, altered mental status, psychiatric features, cranial nerve abnormality, meningeal signs, focal motor weakness, Babinski’s sign, movement disorder, and sensory abnormalities. CONCLUSION: In the absence of definitive diagnostic testing in a potential organ donor, infectious encephalitis can be predicted with a risk score. The risk calculator presented in this paper represents a prototype, establishing a framework that can be expanded to other infectious diseases transmissible through solid organ transplantation. This article is protected by copyright. All rights reserved.

    • Immunity and Immunization
      1. [No abstract]

      2. BACKGROUND: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series; a two-dose series is now recommended in some age groups and there is interest in possible one-dose vaccination. METHODS: We conducted a systematic literature review of HPV vaccine effectiveness by number of doses, including assessment of biases and impact of varying buffer periods (time between vaccination and outcome counting). RESULTS: Of 3787 articles identified, 26 full articles were assessed and 14 included in our review. All studies were conducted within the context of recommended three-dose schedules of bivalent (3) or quadrivalent HPV vaccine (11). Two evaluated effectiveness for prevention of HPV prevalence, six anogenital warts, and six abnormal cervical cytology or histology. Many studies found differences between three-, two- and one-dose vaccine recipients, indicating possible differences in HPV exposure prior to vaccination or in risk behavior. Adjusted or stratified analyses were conducted to control for potential confounding. All studies found significant vaccine effectiveness with three doses, 11 with two doses at various intervals, and six with one dose. Most studies showed a relationship (not always statistically significant) between effectiveness and number of doses, with greater decreases in HPV-related outcomes with three, followed by two and one dose(s). Few studies conducted formal comparisons of three vs fewer doses. Three of four studies that examined buffer periods found higher effectiveness and a smaller difference by number of doses with longer periods. CONCLUSION: Most post-licensure studies report highest effectiveness with three doses; some found no statistically significant difference between two and three doses. Additionally, almost half found some effectiveness with one dose. Several biases impact estimates, with most biasing two- and one-dose results away from showing effectiveness. Future effectiveness studies, examining persons vaccinated prior to sexual activity and using methods to reduce potential sources of bias, can help inform vaccination policy.

      3. Provider insight on surmounting specialty practice challenges to improve Tdap immunization rates among pregnant womenExternal
        Mehrotra A, Fisher AK, Mullen J, Rodriguez L, Jiles AJ, Albert AP, Randall LA, Frew PM.
        Heliyon. 2018 ;4(5).

        Background: Pertussis, or “whooping cough,” is an acute, contagious pulmonary disease that, despite being vaccine-preventable, has become an increasingly widespread problem in the United States. As a result, the Advisory Committee on Immunization Practices and American College of Obstetricians and Gynecologists updated recommendations stating clinicians should give a Tdap dose during every pregnancy, preferably at 27-36 weeks. Despite this recommendation, reported Tdap vaccine receipt rates during pregnancy vary from 16-61%, and previous studies have shown that clinician recommendation and vaccine administration are strongly associated with vaccine uptake among pregnant women. Methods: Our aim was to inform new strategies to increase uptake of the Tdap vaccine among pregnant women and, ultimately, reduce pertussis-related morbidity and mortality in infants. We conducted interviews with a sample of 24 ob-gyns. We subsequently performed grounded theory analyses of transcripts using deductive and inductive coding strategies followed by intercoder reliability assessment. Results: All physicians interviewed were familiar with the most recent recommendation of giving the Tdap vaccine during the third trimester of every pregnancy, and the majority of physicians stated that they felt that the vaccine was important and effective due to the transfer of pertussis antibodies from the mother to the fetus. Most physicians indicated that they recommended the vaccine to patients during pregnancy, but not all reported administering it on site because it was not stocked at their practice. Implementation challenges for physicians included insurance reimbursement and other challenges (i.e., patient refusal). Tdap vaccination during pregnancy was a lower clinical priority for some physicians. Physicians recognized the benefits associated with Tdap vaccination during pregnancy. Conclusions: Findings indicate while most ob-gyns recognize the benefits of Tdap and recommend vaccination during pregnancy, barriers such as insurance reimbursement and financial concerns for the practice can outweigh the perceived benefits. This resulted in some ob-gyns reporting choosing not to stock and administer the vaccine in their practice. Recommendations to address these concerns include 1) structural support for Tdap vaccine administration in ob-gyns practices; 2) Continuing medical education-equivalent educational interventions that address management techniques, vaccine coding, and other relevant information; and 3) interventions to assist physicians in communicating the importance of Tdap vaccination during pregnancy.

      4. Notes from the field: Vaccine administration errors involving recombinant zoster vaccine – United States, 2017-2018External
        Shimabukuro TT, Miller ER, Strikas RA, Hibbs BF, Dooling K, Goud R, Cano MV.
        MMWR Morb Mortal Wkly Rep. 2018 May 25;67(20):585-586.

        [No abstract]

      5. Vaccination coverage among children aged 2 years – U.S. Affiliated Pacific Islands, April-October, 2016External
        Tippins A, Murthy N, Meghani M, Solsman A, Apaisam C, Basilius M, Eckert M, Judicpa P, Masunu Y, Pistotnik K, Pedro D, Sasamoto J, Underwood JM.
        MMWR Morb Mortal Wkly Rep. 2018 May 25;67(20):579-584.

        Vaccine-preventable diseases (VPDs) cause substantial morbidity and mortality in the United States Affiliated Pacific Islands (USAPI).* CDC collaborates with USAPI immunization programs to monitor vaccination coverage. In 2016, (dagger) USAPI immunization programs and CDC piloted a method for estimating up-to-date status among children aged 2 years using medical record abstraction to ascertain regional vaccination coverage. This was the first concurrent assessment of childhood vaccination coverage across five USAPI jurisdictions (American Samoa; Chuuk State, Federated States of Micronesia [FSM]; Commonwealth of the Northern Mariana Islands [CNMI]; Republic of the Marshall Islands [RMI]; and Republic of Palau).( section sign) Differences in vaccination coverage between main and outer islands( paragraph sign) were assessed for two jurisdictions where data were adequate.** Series coverage in this report includes the following doses of vaccines: >/=4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP); >/=3 doses of inactivated poliovirus vaccine (IPV); >/=1 dose of measles, mumps, and rubella vaccine (MMR); >/=3 doses of Haemophilus influenzae type B (Hib) vaccine; >/=3 doses of hepatitis B (HepB) vaccine; and >/=4 doses of pneumococcal conjugate vaccine (PCV); i.e., 4:3:1:3:3:4. Coverage with >/=3 doses of rotavirus vaccine was also assessed. Completion of the recommended series of each of these vaccines(daggerdagger) was <90% in all jurisdictions except Palau. Coverage with the full recommended six-vaccine series (4:3:1:3:3:4) ranged from 19.5% (Chuuk) to 69.1% (Palau). In RMI and Chuuk, coverage was lower in the outer islands than in the main islands for most vaccines, with differences ranging from 0.9 to 66.8 percentage points. Medical record abstraction enabled rapid vaccination coverage assessment and timely dissemination of results to guide programmatic decision-making. Effectively monitoring vaccination coverage, coupled with implementation of data-driven interventions, is essential to maintain protection from VPD outbreaks in the region and the mainland United States.

    • Injury and Violence
      1. Engendering healthy masculinities to prevent sexual violence: Rationale for and design of the Manhood 2.0 trialExternal
        Abebe KZ, Jones KA, Culyba AJ, Feliz NB, Anderson H, Torres I, Zelazny S, Bamwine P, Boateng A, Cirba B, Detchon A, Devine D, Feinstein Z, Macak J, Massof M, Miller-Walfish S, Morrow SE, Mulbah P, Mulwa Z, Paglisotti T, Ripper L, Ports KA, Matjasko JL, Garg A, Kato-Wallace J, Pulerwitz J, Miller E.
        Contemp Clin Trials. 2018 May 23.

        Violence against women and girls is an important global health concern. Numerous health organizations highlight engaging men and boys in preventing violence against women as a potentially impactful public health prevention strategy. Adapted from an international setting for use in the US, “Manhood 2.0” is a “gender transformative” program that involves challenging harmful gender and sexuality norms that foster violence against women while promoting bystander intervention (i.e., giving boys skills to interrupt abusive behaviors they witness among peers) to reduce the perpetration of sexual violence (SV) and adolescent relationship abuse (ARA). Manhood 2.0 is being rigorously evaluated in a community-based cluster-randomized trial in 21 lower resource Pittsburgh neighborhoods with 866 adolescent males ages 13-19. The comparison intervention is a job readiness training program which focuses on the skills needed to prepare youth for entering the workforce, including goal setting, accountability, resume building, and interview preparation. This study will provide urgently needed information about the effectiveness of a gender transformative program, which combines healthy sexuality education, gender norms change, and bystander skills to interrupt peers’ disrespectful and harmful behaviors to reduce SV/ARA perpetration among adolescent males. In this manuscript, we outline the rationale for and evaluation design of Manhood 2.0. Clinical Trials #: NCT02427061.

    • Laboratory Sciences
      1. Laboratory tests were carried out to examine the efficacy of different exposure intervals (2 h, 4 h, 8 h, 1 d, 2 d, 3 d, and 7 d) on different life stages (adults, pupae, larvae, and eggs) of Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae), the confused flour beetle, and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae), the saw-toothed grain beetle (adults, larvae, and eggs) to 0, -5, -10, and -15 degrees C. Larvae and pupae of T. confusum were more cold-tolerant than eggs or adults. Exposure to temperatures of -10 degrees C for 1 d will kill nearly 100% of all life stages of T. confusum. O. surinamensis was more cold-tolerant than T. confusum. Adults of O. surinamensis were not killed when exposed for 1 d at -5 degrees C, but egg hatch was drastically reduced after 2 h of exposure at the same temperature. Eggs and adults of O. surinamensis were more cold-tolerant than larvae. Our study indicates that target insect species and life stage, temperature, and exposure interval should all be considered when cold treatment is selected as a control strategy against T. confusum and O. surinamensis. Facility managers can use these data in planning cold treatments.

      2. Ferrets as models for influenza virus transmission studies and pandemic risk assessmentsExternal
        Belser JA, Barclay W, Barr I, Fouchier RA, Matsuyama R, Nishiura H, Peiris M, Russell CJ, Subbarao K, Zhu H, Yen HL.
        Emerg Infect Dis. 2018 Jun;24(6):965-971.

        The ferret transmission model is extensively used to assess the pandemic potential of emerging influenza viruses, yet experimental conditions and reported results vary among laboratories. Such variation can be a critical consideration when contextualizing results from independent risk-assessment studies of novel and emerging influenza viruses. To streamline interpretation of data generated in different laboratories, we provide a consensus on experimental parameters that define risk-assessment experiments of influenza virus transmissibility, including disclosure of variables known or suspected to contribute to experimental variability in this model, and advocate adoption of more standardized practices. We also discuss current limitations of the ferret transmission model and highlight continued refinements and advances to this model ongoing in laboratories. Understanding, disclosing, and standardizing the critical parameters of ferret transmission studies will improve the comparability and reproducibility of pandemic influenza risk assessment and increase the statistical power and, perhaps, accuracy of this model.

      3. Genotype I of Japanese encephalitis virus virus-like particles elicit sterilizing immunity against genotype I and III viral challenge in swineExternal
        Fan YC, Chen JM, Lin JW, Chen YY, Wu GH, Su KH, Chiou MT, Wu SR, Yin JH, Liao JW, Chang GJ, Chiou SS.
        Sci Rep. 2018 May 10;8(1):7481.

        Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine. A CHO-heparan sulfate-deficient (CHO-HS(-)) cell clone, named 51-10 clone, stably expressing GI-JEV VLP was selected and continually secreted GI VLPs without signs of cell fusion. 51-10 VLPs formed a homogeneously empty-particle morphology and exhibited similar antigenic activity as GI virus. GI VLP-immunized mice showed balanced cross-neutralizing antibody titers against GI to GIV viruses (50% focus-reduction micro-neutralization assay titers 71 to 240) as well as potent protection against GI or GIII virus infection. GI VLP-immunized swine challenged with GI or GIII viruses showed no fever, viremia, or viral RNA in tonsils, lymph nodes, and brains as compared with phosphate buffered saline-immunized swine. We thus conclude GI VLPs can provide sterile protection against GI and GIII viruses in swine.

      4. Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primatesExternal
        Girard L, Birse K, Holm JB, Gajer P, Humphrys MS, Garber D, Guenthner P, Noel-Romas L, Abou M, McCorrister S, Westmacott G, Wang L, Rohan LC, Matoba N, McNicholl J, Palmer KE, Ravel J, Burgener AD.
        Sci Rep. 2018 May 23;8(1):8059.

        Topical microbicides are being explored as an HIV prevention method for individuals who practice receptive anal intercourse. In vivo studies of these microbicides are critical to confirm safety. Here, we evaluated the impact of a rectal microbicide containing the antiviral lectin, Griffithsin (GRFT), on the rectal mucosal proteome and microbiome. Using a randomized, crossover placebo-controlled design, six rhesus macaques received applications of hydroxyethylcellulose (HEC)- or carbopol-formulated 0.1% GRFT gels. Rectal mucosal samples were then evaluated by label-free tandem MS/MS and 16 S rRNA gene amplicon sequencing, for proteomics and microbiome analyses, respectively. Compared to placebo, GRFT gels were not associated with any significant changes to protein levels at any time point (FDR < 5%), but increased abundances of two common and beneficial microbial taxa after 24 hours were observed in HEC-GRFT gel (p < 2E-09). Compared to baseline, both placebo formulations were associated with alterations to proteins involved in proteolysis, activation of the immune response and inflammation after 2 hours (p < 0.0001), and increases in beneficial Faecalibacterium spp. after 24 hours in HEC placebo gel (p = 4.21E-15). This study supports the safety profile of 0.1% GRFT gel as an anti-HIV microbicide and demonstrates that current placebo formulations may associate with changes to rectal proteome and microbiota.

      5. Use of a scalable replicon-particle vaccine to protect against lethal Lassa virus infection in the guinea pig modelExternal
        Kainulainen MH, Spengler JR, Welch SR, Coleman-McCray JD, Harmon JR, Klena JD, Nichol ST, Albarino CG, Spiropoulou CF.
        J Infect Dis. 2018 May 25;217(12):1957-1966.

        Lassa fever is a viral zoonosis that can be transmitted from person to person, especially in the hospital setting. The disease is endemic to several countries in West Africa and can be a major contributor to morbidity and mortality in affected areas. There are no approved vaccines to prevent Lassa virus infection. In this work, we present a vaccine candidate that combines the scalability and efficacy benefits of a live vaccine with the safety benefits of single-cycle replication. The system consists of Lassa virus replicon particles devoid of the virus essential glycoprotein gene, and a cell line that expresses the glycoprotein products, enabling efficient vaccine propagation. Guinea pigs vaccinated with these particles showed no clinical reaction to the inoculum and were protected against fever, weight loss, and lethality after infection with Lassa virus.

      6. Cryptosporidium spp. are opportunistic protozoan parasites that infect epithelial cells in the intestinal tract and cause a flu-like diarrheal illness. Innate immunity is key to limiting the expansion of parasitic stages early in infection. One mechanism in which it does this is through the generation of early cytokines, such as IL-18. The processing and secretion of mature IL-18 (and IL-1beta) is mediated by caspase-1 which is activated within an inflammasome following the engagement of inflammasome-initiating sensors. We examined how the absence of caspase-1 and caspase-11, the adapter protein Asc, and other inflammasome components affects susceptibility to cryptosporidial infection by these and other key cytokines in the gut. We found that Casp-11(-/-)Casp-1(-/-) knockout mice have increased susceptibility to C. parvum infection as demonstrated by the 35-fold higher oocyst production (at peak infection) compared to wild-type mice. Susceptibility correlated with a lack of IL-18 in caspase-1 and caspase1/11 knockout mice, whereas IL-18 is significantly elevated in wildtype mice. IL-1beta was not generated in any significant amount following infection nor was any increased susceptibility observed in IL-1beta knockout mice. We also show that the adapter protein Asc is important to susceptibility, and that the caspase-1 canonical inflammasome signaling pathway is the dominant pathway in C. parvum resistance.

      7. The neuroinflammatory phenotype in a mouse model of Gulf War Illness is unrelated to brain regional levels of acetylcholine as measured by quantitative HILIC-UPLC-MS/MSExternal
        Miller JV, LeBouf RF, Kelly KA, Michalovicz LT, Ranpara A, Locker AR, Miller DB, O’Callaghan JP.
        Toxicol Sci. 2018 May 28.

        Many veterans of the 1991 Persian Gulf War (GW) returned with a chronic multisymptom illness that has been termed Gulf War Illness (GWI). Previous GWI studies have suggested that exposure to acetylcholinesterase inhibitors (AChEIs) in theater, such as sarin and/or pesticides, may have contributed to the symptomatology of GWI. Additionally, concomitant high physiological stress experienced during the war may have contributed to the initiation of the GWI phenotype. While inhibition of AChE leading to accumulation of acetylcholine (ACh) will activate the cholinergic anti-inflammatory pathway, the signature symptomatology of GWI has been shown to be associated with neuroinflammation. To investigate the relationship between ACh and neuroinflammation in discrete brain regions, we used our previously established mouse model of GWI, which combines an exposure to a high physiological stress mimic, corticosterone (CORT), with GW-relevant AChEIs. The AChEIs used in this study were diisopropyl fluorophosphate (DFP), chlorpyrifos oxon (CPO), and physostigmine (PHY). After AChEI exposure, ACh concentrations for cortex (CTX), hippocampus (HIP), and striatum (STR) were determined using hydrophilic interaction liquid chromatography (HILIC) with ultra-performance liquid chromatography (UPLC)-tandem-mass spectrometry (MS/MS). CORT pretreatment ameliorated the DFP-induced ACh increase in HIP and STR, but not CTX. CORT pretreatment did not significantly alter ACh levels for CPO and PHY. Further analysis of STR neuroinflammatory biomarkers revealed an exacerbated CORT+AChEI response, which does not correspond to measured brain ACh. By utilizing this new analytical method for discrete brain region analysis of ACh, this work suggests the exacerbated neuroinflammatory effects in our mouse model of GWI are not driven by the accumulation of brain region-specific ACh.

      8. Performance of the Alere Determine HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimensExternal
        Parker MM, Bennett SB, Sullivan TJ, Fordan S, Wesolowski LG, Wroblewski K, Gaynor AM.
        J Clin Virol. 2018 May 14;104:89-91.

        BACKGROUND: The capacity of HIV Antigen/Antibody (Ag/Ab) immunoassays (IA) to detect HIV-1 p24 antigen has resulted in improved detection of HIV-1 infections in comparison to Ab-only screening assays. Since its introduction in the US, studies have shown that the Determine HIV-1/2 Ag/Ab Combo assay (Determine Ag/Ab) detects HIV infection earlier than laboratory-based IgM/IgG-sensitive IAs, but its sensitivity for HIV-1 p24 Ag detection is reduced compared to laboratory-based Ag/Ab assays. However, further evaluation is needed to assess its capacity to detect acute HIV-1 infection. OBJECTIVE: To assess the performance of Determine Ag/Ab in serum from acute HIV-1 infections. STUDY DESIGN: Select serum specimens that screened reactive on a laboratory-based Ag/Ab IA or IgM/IgG Ab-only IA, with a negative or indeterminate supplemental antibody test and detectable HIV-1 RNA were retrospectively tested with Determine Ag/Ab. Results were compared with those of the primary screening immunoassay to evaluate concordance within this set of algorithm-defined acute infections. RESULTS: Of 159 algorithm-defined acute HIV-1 specimens, Determine Ag/Ab was reactive for 105 resulting in 66.0% concordance. Of 125 that were initially detected by a laboratory-based Ag/Ab IA, 81 (64.8%) were reactive by Determine Ag/Ab. A total of 34 acute specimens were initially detected by a laboratory-based IgM/IgG Ab-only IA and 24 (70.6%) of those were reactive by Determine Ag/Ab. CONCLUSIONS: Due to their enhanced sensitivity, laboratory-based Ag/Ab IAs continue to be preferred over the Determine Ag/Ab as the screening method used by laboratories conducting HIV diagnostic testing on serum and plasma specimens.

      9. Quantitative HPLC-MS/MS analysis of toxins in soapberry seeds: Methylenecyclopropylglycine and hypoglycin AExternal
        Sanford AA, Isenberg SL, Carter MD, Mojica MA, Mathews TP, Harden LA, Takeoka GR, Thomas JD, Pirkle JL, Johnson RC.
        Food Chemistry. 2018 ;264:449-454.

        Methylenecyclcopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in various soapberry (Sapindaceae) fruits. These toxins have been linked to illnesses worldwide and were recently implicated in Asian outbreaks of acute hypoglycemic encephalopathy. In a previous joint agricultural and public health investigation, we developed an analytical method capable of evaluating MCPG and HGA concentrations in soapberry fruit arils as well as a clinical method for the urinary metabolites of the toxins. Since the initial soapberry method only analyzed the aril portion of the fruit, we present here the extension of the method to include the fruit seed matrix. This work is the first method to quantitate both MCPG and HGA concentrations in the seeds of soapberry fruit, including those collected during a public health investigation. Further, this is the first quantitation of HGA in litchi seeds as well as both toxins in mamoncillo and longan seeds.

      10. Pathogenesis and transmission of genetically diverse swine-origin H3N2v influenza A viruses from multiple lineages isolated in the United States, 2011-2016External
        Sun X, Pulit-Penaloza JA, Belser JA, Pappas C, Pearce MB, Brock N, Zeng H, Creager HM, Zanders N, Jang Y, Tumpey TM, Davis T, Maines TR.
        J Virol. 2018 May 30.

        While several swine-origin influenza A H3N2 variant (H3N2v) viruses isolated from humans prior to 2011 have been previously characterized for their virulence and transmissibility in ferrets, recent genetic and antigenic divergence of H3N2v viruses warrants an updated assessment of their pandemic potential. Here, four contemporary H3N2v viruses isolated during 2011-2016 were evaluated for their replicative ability in both in vitro and in vivo mammalian models, as well as their transmissibility among ferrets. We found that all four H3N2v viruses possessed similar or enhanced replication capacity in a human bronchial epithelium cell line (Calu-3) compared to a human seasonal influenza virus, suggestive of strong fitness in human respiratory tract cells. The majority of H3N2v viruses examined in our study were mildly virulent in mice and capable of replicating in mouse lungs with different degrees of efficiency. In ferrets, all four H3N2v viruses caused moderate morbidity and exhibited comparable titers in the upper respiratory tract, but only 2 of the 4 viruses replicated in the lower respiratory tract in this model. Furthermore, despite efficient transmission among cohoused ferrets, recently isolated H3N2v viruses displayed considerable variance in their ability to transmit by respiratory droplets. The lack of a full understanding of the molecular correlates of virulence and transmission underscores the need for close genotypic and phenotypic monitoring of H3N2v viruses and the importance of continued surveillance to improve pandemic preparedness.Importance: Swine-origin influenza viruses of the H3N2 subtype, with the HA and NA derived from historic human seasonal influenza viruses, continue to cross species barriers and cause human infections, posing an indelible threat to public health. To help us better understand the potential risk associated with swine-origin H3N2v viruses that emerged in the U.S between 2011-2016 influenza seasons, we use both in vitro and in vivo models to characterize the ability of these viruses to replicate, caused disease, and transmit in mammalian hosts. The efficient respiratory droplet transmission exhibited by some of the H3N2v viruses in the ferret model combined with the existing evidence of low immunity against such viruses in young children and older adults highlights their pandemic potential. Extensive surveillance and risk assessment of H3N2v viruses should continue to be an essential component of our pandemic preparedness strategy.

      11. Background: Harmonizing critical reagents for the folate microbiological assay (MBA) may improve among-laboratory comparability. Objective:We assessed the comparability of the MBA for serum folate (S-FOL) and whole-blood folate (WB-FOL) in an international comparison study. Methods: Eight laboratories obtained a kit containing CDC microorganism inoculum (chloramphenicol-resistant Lactobacillus rhamnosus), CDC calibrator (5-methyltetrahydrofolate), and 23 serum and WB hemolysate samples each. Laboratories analyzed the samples in single measurement over 2 d using 4 conditions: in-house microorganism and in-house calibrator (IH-MO & IH-CAL), in-house microorganism and CDC calibrator (IH-MO & CDC-CAL), CDC microorganism and in-house calibrator (CDC-MO & IH-CAL), and CDC microorganism and CDC calibrator (CDC-MO & CDC-CAL). We calculated geometric mean concentrations for each laboratory and condition and compared data to the CDC MBA (target). Results: The among-laboratory arithmetic mean S-FOL concentrations for the 4 conditions were 30.2, 28.1, 30.0, and 29.9 (group 1, 5-methyltetrahydrofolate IH-CAL) compared with 35.3, 33.3, 33.6, and 30.7 nmol/L (group 2, folic acid IH-CAL), respectively; and 428, 405, 398, and 393 (group 1) compared with 469, 423, 477, and 418 nmol/L (group 2), respectively, for WB-FOL. Differences to the CDC MBA target values were smaller for group 1 (range across conditions; S-FOL: 9.9-21%; WB-FOL: 9.0-18%) compared with group 2 laboratories (S-FOL: 13-30%; WB-FOL: 16-32%) and smaller when CDC reagents were used compared with in-house reagents (S-FOL: 12% compared with 22%; WB-FOL: 13%compared with 25%). A linear mixed model estimated a small microorganism effect (S-FOL: 2.3%; WB-FOL: 2.3%) and a larger mean calibrator effect; folic acid compared with 5-methyltetrahydrofolate calibrator produced 12%higher SFOL and 15%higher WB-FOL results. When laboratories used CDC reagents, the estimated among-laboratory variability was ~10% for S-FOL and WB-FOL. Conclusion: Harmonizing the calibrator and microorganism for the folate MBA has the potential to improve the amonglaboratory comparability in future surveys.

      12. Analysis of crystalline silica aerosol using portable raman spectrometry: Feasibility of near real-time measurementExternal
        Zheng L, Kulkarni P, Birch ME, Ashley K, Wei S.
        Analytical Chemistry. 2018 2018/05/15;90(10):6229-6239.

        A Raman spectroscopy based method has been developed for measurement of trace airborne concentrations of respirable crystalline silica (RCS) using various aerosol sampling and analysis techniques. Three aerosol microconcentration techniques were investigated for effective coupling of collected particulate samples with micro-Raman spectroscopy: (i) direct analysis on a particulate filter after focused aerosol collection using a converging nozzle; (ii) analysis of dried particulate deposit on a filter obtained directly from the aerosol phase using the Spotsampler device; and (iii) analysis of a dried spot (approximately 1.3 mm diameter) obtained by redepositing the particulate sample, after low-temperature plasma ashing of the filter sample. The deposition characteristics (i.e., spot diameter, shape, and deposit uniformity) of each technique were investigated. Calibration curves were constructed and detection limits were estimated for alpha-quartz using the A1 Raman Si-O-Si stretching-bending phonon mode at 465 cm-1. The measurement sensitivity could be substantially improved by increasing the signal integration time and by reducing the particle deposition area. Detection limits in the range of 8-55 ng could be achieved by microconcentrating the aerosol sample over a spot measuring 400-1000 microm in diameter. These detection limits were two to three orders of magnitude lower compared to those attainable using current standardized X-ray diffraction and infrared spectroscopy methods. The low detection limits suggest that near real-time measurements of RCS could be achieved with limits of quantification ranging from 2 to 18.5 microg/m3 (at 10 min collection time and 1.2 L/min sampling flow rate), depending on microconcentration technique used. The method was successfully extended to the measurement of alpha-quartz air concentration in representative workplace aerosol samples. This study demonstrates the potential of portable micro-Raman spectroscopy for near-real time measurement of trace RCS in air.

    • Maternal and Child Health
      1. Trends in rooming-in practices among hospitals in the United States, 2007-2015External
        Barrera CM, Nelson JM, Boundy EO, Perrine CG.
        Birth. 2018 May 27.

        BACKGROUND: Rooming-in, or keeping mothers and infants together throughout the birth hospitalization, increases breastfeeding initiation and duration, and is one of the Ten Steps to Successful Breastfeeding. METHODS: The Centers for Disease Control and Prevention’s (CDC) Maternity Practices in Infant Nutrition and Care (mPINC) survey is a biennial census of all birth facilities in the United States and its territories. Data from the 2007-2015 mPINC surveys were used to assess trends in the prevalence of hospitals with most (>/=90%) infants rooming-in more than 23 hours per day (ideal practice). Hospital practices among breastfed infants not rooming-in at night and reasons why hospitals without ideal rooming-in practices removed healthy, full-term, breastfed infants from their mothers’ rooms were also analyzed. RESULTS: The percentage of hospitals with ideal practice increased from 27.8% in 2007 to 51.4% in 2015. Most breastfed infants who were not rooming-in were brought to their mothers at night for feedings (91.8% in 2015). Among hospitals without ideal rooming-in practices, the percentage removing 50% or more of infants from their mothers’ rooms at any point during the hospitalization decreased for all reasons surveyed during 2007-2015; however, in 2015, hospitals still reported regularly removing infants for hearing tests (73.2%), heel sticks (65.5%), infant baths (40.2%), pediatric rounds (35.5%), and infant photos (25.4%). CONCLUSIONS: Hospital implementation of rooming-in increased 23.6 percentage points during 2007-2015. Continued efforts are needed to ensure that all mothers who choose to breastfeed receive optimal lactation support during the first days after giving birth.

      2. [No abstract]

      3. Comparison of state risk-appropriate neonatal care policies with the 2012 AAP policy statementExternal
        Kroelinger CD, Okoroh EM, Goodman DA, Lasswell SM, Barfield WD.
        J Perinatol. 2018 Apr;38(4):411-420.

        OBJECTIVE: Compare state policies with standards outlined in the 2012 AAP Policy Statement on Levels of Neonatal Care. STUDY DESIGN: Systematic, web-based review of publicly available policies on levels of care in all states in 2014. Infant risk information, equipment capabilities, and specialty staffing were abstracted from published rules, statutes, and regulations. RESULT: Twenty-two states had a policy on regionalized perinatal care. State policies vary in consistency with the AAP Policy, with 60% of states including standards consistent with Level I criteria, 48% Level II, 14% Level III, and one state with Level IV. Ventilation capability standards are highly consistent (66-100%), followed by imaging capability standards (50-90%). Policy language on specialty staffing (44-68%), and subspecialty staffing (39-50%) are moderately consistent. CONCLUSION: State policies vary in consistency, a potentially significant barrier to monitoring, regulation, uniform care provision and measurement, and reporting of national-level measures on risk-appropriate care.

      4. Bladder management and continence outcomes in adults with spina bifida: Results from the National Spina Bifida Patient Registry, 2009 to 2015External
        Wiener JS, Suson KD, Castillo J, Routh JC, Tanaka ST, Liu T, Ward EA, Thibadeau JK, Joseph DB.
        J Urol. 2018 Mar 26.

        PURPOSE: Most children with spina bifida now survive into adulthood, although most have neuropathic bladder with potential complications of incontinence, infection, renal damage and diminished quality of life. In this study we sought to 1) describe contemporary bladder management and continence outcomes of adults with spina bifida, 2) describe differences from younger individuals and 3) assess for association with socioeconomic factors. MATERIALS AND METHODS: We analyzed data on bladder management and outcomes in adults with spina bifida from the National Spina Bifida Patient Registry. A strict definition of continence was used. Results were compared to young children (age 5 to 11 years) and adolescents (12 to 19). Statistical analysis compared cohorts by gender, ethnicity, spina bifida type, lesion level, insurance status, educational attainment, employment status and continence. RESULTS: A total of 5,250 patients with spina bifida were included, of whom 1,372 (26.1%) were adults. Of the adult patients 45.8% did not take medication, but 76.8% performed clean intermittent catheterization. Continence was decreased in adults with myelomeningocele (45.8%) vs those with nonmyelomeningocele spina bifida (63.1%, p <0.0001). Continence rates were higher in the older cohorts with myelomeningocele (p <0.0001) but not in those with nonmyelomeningocele spina bifida (p = 0.1192). Bladder management and history of urological surgery varied among age groups. On univariate analysis with spina bifida related or socioeconomic variables continence was significantly associated with educational level but on multivariable logistic regression analysis bladder continence was significantly associated with employment status only. CONCLUSIONS: Bladder management techniques differ between adults and children with spina bifida. Bladder continence outcomes were better in adults, with nearly half reporting continence. Continence was significantly associated with employment status in patients age 25 years or older.

    • Obituary
      1. In Memoriam, Fred Gordin, MD, 1951-2018External
        Cohn DL, El Sadr WM, Abrams DI, Neaton JD, Benator DA, Vernon AA.
        Clin Infect Dis. 2018 May 29.

        [No abstract]

    • Occupational Safety and Health
      1. Elevated depressive symptoms among hired crop workers in the United States: Variation by sociodemographic and employment characteristicsExternal
        Alterman T, Grzywacz JG, Muntaner C, Shen R, Gabbard S, Georges A, Nakamoto JM, Carroll DJ.
        J Rural Ment Health. 2018 May.

        We present prevalence rates, along with demographic and economic characteristics associated with elevated depressive symptoms (EDS), in a nationally representative sample of hired crop workers in the United States. We analyzed in-person interviews with 3,691 crop workers collected in 2009-2010 as part of a mental health and psychosocial supplement to the National Agricultural Workers Survey. The prevalence of EDS was 8.3% in men and 17.1% in women. For men, multivariate analysis showed that EDS was associated with years of education, family composition, having a great deal of difficulty being separated from family, having fair or poor general health, ability to read English, fear of being fired from their current farm job, and method of payment (piece, salary, or a combination). Interactions were found between region of the country and family composition. Multivariate analyses for women showed that fear of being fired, fair or poor general health, having children <=15 years of age, being unaccompanied by their nuclear family, expectation for length of time continuing to do farm work in the United States, and authorization status were associated with EDS. Interactions were found with Hispanic ethnicity and region of the country, as well as presence of the nuclear family and region. The present study identifies important risk factors in this first population-based assessment of EDS in a nationally representative sample of U.S. crop workers. The importance of social support from family, job insecurity, and high prevalence of EDS in female crop workers support the need for screening and outreach in this primarily rural group of men and women crop workers.

      2. Supporting a culture of health in the workplace: A review of evidence-based elementsExternal
        Flynn JP, Gascon G, Doyle S, Matson Koffman DM, Saringer C, Grossmeier J, Tivnan V, Terry P.
        Am J Health Promot. 2018 Jan 1:890117118761887.

        OBJECTIVE: To identify and evaluate the evidence base for culture of health elements. DATA SOURCE: Multiple databases were systematically searched to identify research studies published between 1990 and 2015 on culture of health elements. STUDY INCLUSION AND EXCLUSION CRITERIA: Researchers included studies based on the following criteria: (1) conducted in a worksite setting; (2) applied and evaluated 1 or more culture of health elements; and (3) reported 1 or more health or safety factors. DATA EXTRACTION: Eleven researchers screened the identified studies with abstraction conducted by a primary and secondary reviewer. Of the 1023 articles identified, 10 research reviews and 95 standard studies were eligible and abstracted. DATA SYNTHESIS: Data synthesis focused on research approach and design as well as culture of health elements evaluated. RESULTS: The majority of published studies reviewed were identified as quantitative studies (62), whereas fewer were qualitative (27), research reviews (10), or other study approaches. Three of the most frequently studied culture of health elements were built environment (25), policies and procedures (28), and communications (27). Although all studies included a health or safety factor, not all reported a statistically significant outcome. CONCLUSIONS: A considerable number of cross-sectional studies demonstrated significant and salient correlations between culture of health elements and the health and safety of employees, but more research is needed to examine causality.

      3. The effects of feed force on rivet bucking bar vibrationsExternal
        McDowell TW, Xu XS, Warren C, Welcome DE, Dong RG.
        Int J Ind Ergon. 2018 ;67:145-158.

        Percussive riveting is the primary process for attaching the outer sheet metal “skins” of an aircraft to its airframe. Workers using manually-operated riveting tools (riveting hammers and rivet bucking bars) are exposed to significant levels of hand-transmitted vibration (HTV) and are at risk of developing components of hand-arm vibration syndrome (HAVS). To protect workers, employers can assess and select riveting tools that produce reduced HTV exposures. Researchers at the National Institute for Occupational Safety & Health (NIOSH) have developed a laboratory-based apparatus and methodology to evaluate the vibrations of rivet bucking bars. Using this simulated riveting approach, this study investigated the effects of feed force on the vibrations of several typical rivet bucking bars and that transmitted to the bucking bar operator’s wrist. Five bucking bar models were assessed under three levels of feed force. The study results demonstrate that the feed force can be a major influencing factor on bucking bar vibrations. Similar feed force effects were observed at the bucking bar operator’s wrist. This study also shows that different bucking bar designs will respond differently to variations in feed force. Some bucking bar designs may offer reduced vibration exposures to the bar operator’s fingers while providing little attenuation of wrist acceleration. Knowledge of how rivet bucking bar models respond to riveting hammer vibrations can be important for making informed bucking bar selections. The study results indicate that, to help in the appropriate selection of bucking bars, candidate bar models should be evaluated at multiple feed force levels. The results also indicate that the bucking bar model, feed force level, or the bucking bar operator have no meaningful effects on the vibration excitation (riveting hammer), which further suggests that the test apparatus proposed by NIOSH researchers meets the basic requirements for a stable vibration source in laboratory-based bucking bar vibration assessments. This study provides relevant information that can be used to help develop a standardized laboratory-based bucking bar evaluation methodology and to help in the selection of appropriate bucking bars for various workplace riveting applications. Relevance to Industry: Because the feed force level can affect HTV exposures to bucking bar operators, the feed force required for specific riveting operations should be an important consideration when selecting bucking bar models. This study provides useful information about bucking bar responses to riveting hammer vibrations; this knowledge can improve bucking bar selections.

    • Parasitic Diseases
      1. Angiostrongylus cantonensis infection of central nervous system, Guiana ShieldExternal
        Defo AL, Lachaume N, Cuadro-Alvarez E, Maniassom C, Martin E, Njuieyon F, Henaff F, Mrsic Y, Brunelin A, Epelboin L, Blanchet D, Harrois D, Desbois-Nogard N, Qvarnstrom Y, Demar M, Dard C, Elenga N.
        Emerg Infect Dis. 2018 Jun;24(6):1153-1155.

        We report a case of eosinophilic meningitis complicated by transverse myelitis caused by Angiostrongylus cantonensis in a 10-year-old boy from Brazil who had traveled to Suriname. We confirmed diagnosis by serology and real-time PCR in the cerebrospinal fluid. The medical community should be aware of angiostrongyliasis in the Guiana Shield.

      2. Abbreviated atovaquone-proguanil prophylaxis regimens in travellers after leaving malaria-endemic areas: A systematic reviewExternal
        Savelkoel J, Binnendijk KH, Spijker R, van Vugt M, Tan K, Hanscheid T, Schlagenhauf P, Grobusch MP.
        Travel Med Infect Dis. 2018 Jan – Feb;21:3-20.

        BACKGROUND: We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after return as per currently recommended post-travel schedule. METHODS: PubMed and Embase databases were searched to identify relevant studies. This PROSPERO-registered systematic review followed PRISMA guidelines. The search strategy included terms or synonyms relevant to AP combined with terms to identify articles relating to prophylactic use of AP and inhibitory and half-life properties of AP. Studies considered for inclusion were: randomized controlled trials, cohort studies, quasi-experimental studies, open-label trials, patient-control studies, cross-sectional studies; as well as case-series and non-clinical studies. Data on study design, characteristics of participants, interventions, and outcomes were extracted. Primary outcomes considered relevant were prophylactic efficacy and prolonged inhibitory activity and half-life properties of AP. RESULTS: The initial search identified 1,482 publications, of which 40 were selected based on screening. Following full text review, 32 studies were included and categorized into two groups, namely studies in support of the current post-travel regimen (with a total of 2,866 subjects) and studies in support of an alternative regimen (with a total of 533 subjects). CONCLUSION: There is limited direct and indirect evidence to suggest that an abbreviated post-travel regimen for AP may be effective. Proguanil, however, has a short half-life and is essential for the synergistic effect of the combination. Stopping AP early may result in mono-prophylaxis with atovaquone and possibly select for atovaquone-resistant parasites. Furthermore, the quality of the studies in support of the current post-travel regimen outweighs the quality of the studies in support of an alternative short, post-travel regimen, and the total sample size of the studies to support stopping AP early comprises a small percentage of the total sample size of the studies performed to establish the efficacy of the current AP regimen. Additional research is required – especially from studies evaluating impact on malaria parasitaemia and clinical illness and conducted among travellers in high malaria risk settings – before an abbreviated regimen can be recommended in current practice. PROSPERO REGISTRATION NUMBER: CRD42017055244.

    • Program Evaluation
      1. Conducting a large public health data collection project in Uganda: Methods, tools, and lessons learnedExternal
        Stover B, Lubega F, Namubiru A, Bakengesa E, Luboga SA, Makumbi F, Kiwanuka N, Ndizihiwe A, Mukooyo E, Hurley E, Lim T, Borse NN, Bernhardt J, Wood A, Sheppard L, Barnhart S, Hagopian A.
        Journal of Research Practice. 2018 ;14(1).

        We report on the implementation experience of carrying out data collection and other activities for a public health evaluation study on whether U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) investment improved utilization of health services and health system strengthening in Uganda. The retrospective study period focused on the PEPFAR scale-up, from mid-2005 through mid-2011, a period of expansion of PEPFAR programing and health services. We visited 315 health care facilities in Uganda in 2011 and 2012 to collect routine health management information system data forms, as well as to conduct interviews with health system leaders. An earlier phase of this research project collected data from all 112 health district headquarters, reported elsewhere. This article describes the lessons learned from collecting data from health care facilities, project management, useful technologies, and mistakes. We used several new technologies to facilitate data collection, including portable document scanners, smartphones, and web-based data collection, along with older but reliable technologies such as car batteries for power, folding tables to create space, and letters of introduction from appropriate authorities to create entree. Research in limited-resource settings requires an approach that values the skills and talents of local people, institutions and government agencies, and a tolerance for the unexpected. The development of personal relationships was key to the success of the project. We observed that capacity building activities were repaid many fold, especially in data management and technology.

    • Substance Use and Abuse
      1. Notes from the field: Acute poisonings from a synthetic cannabinoid sold as cannabidiol – Utah, 2017-2018External
        Horth RZ, Crouch B, Horowitz BZ, Prebish A, Slawson M, McNair J, Elsholz C, Gilley S, Robertson J, Risk I, Hill M, Fletcher L, Hou W, Peterson D, Adams K, Vitek D, Nakashima A, Dunn A.
        MMWR Morb Mortal Wkly Rep. 2018 May 25;67(20):587-588.

        [No abstract]

      2. Notes from the Field: Outbreak of severe illness linked to the vitamin K antagonist brodifacoum and use of synthetic cannabinoids – Illinois, March-April 2018External
        Moritz E, Austin C, Wahl M, DesLauriers C, Navon L, Walblay K, Hendrickson M, Phillips A, Kerins J, Pennington AF, Lavery AM, El Zahran T, Kauerauf J, Yip L, Thomas J, Layden J.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 1;67(21):607-608.

        [No abstract]

    • Zoonotic and Vectorborne Diseases
      1. Outbreak of severe histoplasmosis among tunnel workers – Dominican Republic, 2015External
        Armstrong PA, Beard JD, Bonilla L, Arboleda N, Lindsley MD, Chae SR, Castillo D, Nunez R, Chiller T, de Perio MA, Pimentel R, Vallabhaneni S.
        Clin Infect Dis. 2018 May 2;66(10):1550-1557.

        Background: Histoplasmosis is a fungal infection associated with exposure to bat guano. An outbreak of an unknown severe febrile illness occurred among tunnel workers in the Dominican Republic, and resulted in several deaths. We conducted an investigation to confirm etiology and recommend control measures. Methods: A case was defined as fever and >/=2 symptoms consistent with histoplasmosis in a tunnel worker, July-September 2015. We interviewed workers and family members, reviewed medical records, tested serum and urine for Histoplasma antigen/antibody, and conducted a cohort study to identify risk factors for histoplasmosis and severe infection (intensive care). Results: A crew of 36 male workers removed large amounts of bat guano from tunnels without respiratory protection for a median of 24 days per worker (range, 1-25 days). Median age was 32 years (range, 18-62 years); none were immunocompromised. Thirty (83%) workers had illness that met the case definition, of whom 28 (93%) were hospitalized, 9 (30%) required intensive care, 6 (20%) required intubation, and 3 (10%) died. The median time from symptom onset to antifungal treatment was 6 days (range, 1-11 days). Twenty-two of 34 (65%) workers had laboratory evidence of infection. Conclusions: Severe illnesses and death likely resulted from exposure to large inocula of Histoplasma capsulatum spores in an enclosed space, lack of respiratory protection, and delay in recognition and treatment. Clinician education about histoplasmosis, improved laboratory capacity to diagnose fungal infections, and occupational health guidance to protect workers against endemic fungi are recommended in the Dominican Republic.

      2. International travel between global urban centres vulnerable to yellow fever transmissionCdc-pdfExternal
        Brent SE, Watts A, Cetron M, German M, Kraemer MU, Bogoch II, Brady OJ, Hay SI, Creatore MI, Khan K.
        Bulletin of the World Health Organization. 2018 ;96(5):343-354, 354A-354B.

        Objective To examine the potential for international travel to spread yellow fever virus to cities around the world. Methods We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers’ destination cities. Findings In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. Conclusion Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics.

      3. Diagnosis of spotted fever group rickettsioses in U.S. travelers returning from Africa, 2007-2016External
        Cherry CC, Denison AM, Kato CY, Thornton K, Paddock CD.
        Am J Trop Med Hyg. 2018 May 29.

        Spotted fever group rickettsioses (SFGRs), such as African tick bite fever (ATBF), are among the most commonly diagnosed diseases for ill travelers returning from southern Africa. We summarized demographic, clinical, and diagnostic features of imported SFGR cases in U.S. travelers returning from Africa who had laboratory specimens submitted to the Centers for Disease Control and Prevention. Diagnosis of SFGR was performed by indirect immunofluorescence antibody assay, immunohistochemical staining, polymerase chain reaction (PCR), or culture. Cases were defined as probable SFGR, confirmed SFGR, or confirmed ATBF. Clinical and epidemiological categorical variables were described as counts and proportions; continuous variables were described using geometric mean titers, median, and range. One hundred and twenty-seven patients satisfied laboratory criteria for confirmed or probable SFGR. Fever was the most common symptom (N = 88; 69%), followed by >/= 1 eschars (N = 70; 55%). Paired serums were submitted for 36 patients (28%); 12 patients (33%) had nonreactive initial serum sample but converted to a titer >/= 64 with the convalescent sample. Twenty-seven patients (21%) had infection with Rickettsia africae based on PCR analysis of eschar swab (N = 8) or biopsy (N = 23). Fifteen patients had eschar biopsy or swab samples and serum sample(s) submitted together; 9 (60%) had PCR-positive eschar results and nonreactive acute serology. Health-care providers should consider SFGR when evaluating patients for a febrile illness with eschar and compatible foreign travel history. Polymerase chain reaction testing of eschar biopsies or swabs provides a confirmed diagnosis in early stages of disease; eschar swabs or biopsies are an underutilized diagnostic technique.

      4. Clinical features of Guillain-Barre syndrome with vs without Zika virus infection, Puerto Rico, 2016External
        Dirlikov E, Major CG, Medina NA, Lugo-Robles R, Matos D, Munoz-Jordan JL, Colon-Sanchez C, Garcia M, Olivero-Segarra M, Malave G, Rodriguez-Vega GM, Thomas DL, Waterman SH, Sejvar JJ, Luciano CA, Sharp TM, Rivera-Garcia B.
        JAMA Neurol. 2018 May 21.

        Importance: The pathophysiologic mechanisms of Guillain-Barre syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective: To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants: During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barre syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. Main Outcomes and Measures: Acute and long-term clinical characteristics of GBS associated with ZIKV infection. Results: Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71.9%]; P = .008), admission to the intensive care unit (47 [66.2%] vs 16 [44.4%]; P = .03), and required mechanical ventilation (22 [31.0%] vs 4 [11.1%]; P = .02). Six months after neurologic illness onset, patients with GBS and evidence of ZIKV infection more frequently reported having excessive or inadequate tearing (30 [53.6%] vs 6 [26.1%]; P = .03), difficulty drinking from a cup (10 [17.9%] vs 0; P = .03), and self-reported substantial pain (15 [27.3%] vs 1 [4.3%]; P = .03). Conclusions and Relevance: In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.

      5. Strengthening of surveillance during monkeypox outbreak, Republic of the Congo, 2017External
        Doshi RH, Guagliardo SA, Dzabatou-Babeaux A, Likouayoulou C, Ndakala N, Moses C, Olson V, McCollum AM, Petersen BW.
        Emerg Infect Dis. 2018 Jun;24(6):1158-1160.

        Reports of 10 suspected cases of monkeypox in Likouala Department, Republic of the Congo, triggered an investigation and response in March 2017 that included community education and surveillance strengthening. Increasing numbers of outbreaks suggest that monkeypox virus is becoming a more prevalent human pathogen. Diverse approaches are necessary for disease control and prevention.

      6. Seroepidemiological studies of arboviruses in AfricaExternal
        Gudo ES, Ali S, Antonio VS, Chelene IR, Chongo I, Demanou M, Falk K, Guiliche OC, Heinrich N, Monteiro V, Muianga AF, Oludele J, Mula F, Mutuku F, Amade N, Alho P, Betsem E, Chimbuinhe Z, Cristovam AJ, Galano G, Gessain A, Harris E, Heise M, Inalda F, Jala I, Jaszi E, King C, Kitron U, Kummerer BM, LaBeaud AD, Lagerqvist N, Malai G, Mazelier M, Mendes S, Mukoko D, Ndenga B, Njouom R, Pinto G, Tivane A, Vu DM, Vulule J.
        Adv Exp Med Biol. 2018 ;1062:361-371.

        The literature on sero-epidemiological studies of flaviviral infections in the African continent is quite scarce. Much of the viral epidemiology studies have been focussing on diseases such as HIV/AIDS because of their sheer magnitude and impact on the lives of people in the various affected countries. Increasingly disease outbreaks caused by arboviruses such as the recent cases of chikungunya virus, dengue virus and yellow fever virus have prompted renewed interest in studying these viruses. International agencies from the US, several EU nations and China are starting to build collaborations to build capacity in many African countries together with established institutions to conduct these studies. The Tofo Advanced Study Week (TASW) was established to bring the best scientists from the world to the tiny seaside town of Praia do Tofo to rub shoulders with African virologists and discuss cutting-edge science and listen to the work of researchers in the field. In 2015 the 1st TASW focussed on Ebola virus. The collections of abstracts from participants at the 2nd TASW which focused on Dengue and Zika virus as well as presentations on other arboviruses are collated in this chapter.

      7. Novel poxvirus in proliferative lesions of wild rodents in East Central Texas, USAExternal
        Hodo CL, Mauldin MR, Light JE, Wilkins K, Tang S, Nakazawa Y, Emerson GL, Ritter JM, Mansell JL, Hamer SA.
        Emerg Infect Dis. 2018 Jun;24(6):1069-1072.

        Northern pygmy mice from 2 localities in East Central Texas, USA, had proliferative epidermal lesions on the tail and feet. Electron microscopy of lesion tissue revealed poxvirus. Phylogenetic analyses indicated the virus differed 35% from its closest relatives, the Chordopoxvirinae. Future research is needed to determine whether this virus could affect human health.

      8. Clothing treated with the pyrethroid permethrin is available in the United States as consumer products to prevent tick bites. We used tick bioassays to quantify contact irritancy and toxicity of permethrin-treated clothing for three important tick vectors of human pathogens: the blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae); the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae); and the American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae). We first demonstrated that field-collected I. scapularis nymphs from Minnesota were as susceptible as laboratory-reared nymphs to a permethrin-treated textile. Field ticks examined in bioassays on the same day they were collected displayed contact irritancy by actively dislodging from a vertically oriented permethrin-treated textile, and a forced 1-min exposure resulted in all ticks being unable to move normally, thus posing no more than minimal risk of biting, 1 h after contact with the treated textile. Moreover, we documented lack of normal movement for laboratory-reared I. scapularis nymphs by 1 h after contact for 1 min with a wide range of permethrin-treated clothing, including garments made from cotton, synthetic materials, and blends. A comparison of the impact of a permethrin-treated textile across tick species and life stages revealed the strongest effect on I. scapularis nymphs (0% with normal movement 1 h after a 1-min exposure), followed by A. americanum nymphs (14.0%), I. scapularis females (38.0%), D. variabilis females (82.0%), and A. americanum females (98.0%). Loss of normal movement for all ticks 1 h after contact with the permethrin-treated textile required exposures of 1 min for I. scapularis nymphs, 2 min for A. americanum nymphs, and 5 min for female I. scapularis, D. variabilis, and A. americanum ticks. We conclude that use of permethrin-treated clothing shows promise to prevent bites by medically important ticks. Further research needs are discussed.

      9. Use of bead-based serologic assay to evaluate chikungunya virus epidemic, HaitiExternal
        Rogier EW, Moss DM, Mace KE, Chang M, Jean SE, Bullard SM, Lammie PJ, Lemoine JF, Udhayakumar V.
        Emerg Infect Dis. 2018 Jun;24(6):995-1001.

        The index case of chikungunya virus (CHIKV) in Haiti was reported during early 2014; the vector, the pervasive Aedes aegypti mosquito, promoted rapid spread throughout the country. During December 2014-February 2015, we collected blood samples from 4,438 persons at 154 sites (62 urban, 92 rural) throughout Haiti and measured CHIKV IgG by using a multiplex bead assay. Overall CHIKV seroprevalence was 57.9%; differences between rural (mean 44.9%) and urban (mean 78.4%) areas were pronounced. Logistic modeling identified the urban environment as a strong predictor of CHIKV exposure (adjusted odds ratio 3.34, 95% CI 2.38-4.69), and geographic elevation provided a strong negative correlation. We observed no correlation between age and antibody positivity or titer. Our findings demonstrated through serologic testing the recent and rapid dissemination of the arbovirus throughout the country. These results show the utility of serologic data to conduct epidemiologic studies of quickly spreading mosquitoborne arboviruses.

      10. Underreporting of Lyme and other tick-borne diseases in residents of a high-incidence county, Minnesota, 2009External
        Schiffman EK, McLaughlin C, Ray JA, Kemperman MM, Hinckley AF, Friedlander HG, Neitzel DF.
        Zoonoses Public Health. 2018 Mar;65(2):230-237.

        Lyme disease (LD), anaplasmosis, babesiosis and other tick-borne diseases (TBDs) attributed to Ixodes ticks are thought to be widely underreported in the United States. To identify TBD cases diagnosed in 2009, but not reported to the Minnesota Department of Health (MDH), diagnostic and procedural billing codes suggestive of tick-borne diseases were used to select medical charts for retrospective review in medical facilities serving residents of a highly endemic county in Minnesota. Of 444 illness events, 352 (79%) were not reported. Of these, 102 (29%) met confirmed or probable surveillance case criteria, including 91 (26%) confirmed LD cases with physician-diagnosed erythema migrans (EM). For each confirmed and probable LD, probable anaplasmosis and confirmed babesiosis case reported to MDH in 2009, 2.8, 1.3, 1.2 and 1.0 cases were likely diagnosed, respectively. These revised estimates provide a more accurate assessment and better understanding of the burden of these diseases in a highly endemic county.

      11. Assessing diagnostic coding practices among a sample of healthcare facilities in Lyme disease endemic areas: Maryland and New York – A Brief ReportExternal
        Thomas N, Rutz HJ, Hook SA, Hinckley AF, Lukacik G, Backenson BP, Feldman KA, White JL.
        Zoonoses Public Health. 2018 Mar;65(2):275-278.

        The value of using diagnostic codes in Lyme disease (LD) surveillance in highly endemic states has not been well studied. Surveys of healthcare facilities in Maryland (MD) and New York (NY) regarding coding practices were conducted to evaluate the feasibility of using diagnostic codes as a potential method for LD surveillance. Most respondents indicated that their practice utilized electronic medical records (53%) and processed medical/billing claims electronically (74%). Most facilities were able to search office visits associated with specific ICD-9-CM and CPT codes (74% and 73%, respectively); no discernible differences existed between the healthcare facilities in both states. These codes were most commonly assigned by the practitioner (82%), and approximately 70% of respondents indicated that these codes were later validated by administrative staff. These results provide evidence for the possibility of using diagnostic codes in LD surveillance. However, the utility of these codes as an alternative to traditional LD surveillance requires further evaluation.

      12. Lyme disease surveillance in New York State: An assessment of case underreportingExternal
        White J, Noonan-Toly C, Lukacik G, Thomas N, Hinckley A, Hook S, Backenson PB.
        Zoonoses Public Health. 2018 Mar;65(2):238-246.

        Despite the mandatory nature of Lyme disease (LD) reporting in New York State (NYS), it is believed that only a fraction of the LD cases diagnosed annually are reported to public health authorities. Lack of complete LD case reporting generally stems from (i) lack of report of provider-diagnosed cases where supportive laboratory testing is not ordered or results are negative (i.e. provider underreporting) and (ii) incomplete case information (clinical laboratory reporting only with no accompanying clinical information) such that cases are considered ‘suspect’ and not included in national and statewide case counts (i.e. case misclassification). In an attempt to better understand LD underreporting in NYS, a two-part study was conducted in 2011 using surveillance data from three counties. Case misclassification was assessed by obtaining medical records on suspect cases and reclassifying according to the surveillance case definition. To assess provider underreporting, lists of patients for whom ICD-9-CM code 088.81 (LD) had been used were reported to NYS Department of Health (NYSDOH). These lists were matched to the NYSDOH case reporting system, and medical records were requested on patients not previously reported; cases were then classified according to the case definition. When including both provider underreporting and case misclassification, approximately 20% (range 18.4-24.6%) more LD cases were identified in the three-county study area than were originally reported through standard surveillance. The additional cases represent a minimum percentage of unreported cases; the true percentage of unreported cases is likely higher. Unreported cases were more likely to have a history of erythema migrans (EM) rash and were more likely to be young paediatric cases. Results of the study support the assertion that LD cases are underreported in NYS. Initiatives to increase reporting should highlight the importance of reporting clinically diagnosed EM and be targeted to those providers most likely to diagnose LD, specifically providers treating paediatric patients.

      13. The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that when compared to the 2013 virus HAs, the fifth wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9)HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth wave H7 HAs analyzed in this study.IMPORTANCE The A(H7N9) viruses circulating in China are of great public health concern. Herein, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.

      14. Reemergence of human monkeypox in Nigeria, 2017External
        Yinka-Ogunleye A, Aruna O, Ogoina D, Aworabhi N, Eteng W, Badaru S, Mohammed A, Agenyi J, Etebu EN, Numbere TW, Ndoreraho A, Nkunzimana E, Disu Y, Dalhat M, Nguku P, Mohammed A, Saleh M, McCollum A, Wilkins K, Faye O, Sall A, Happi C, Mba N, Ojo O, Ihekweazu C.
        Emerg Infect Dis. 2018 Jun;24(6):1149-1151.

        In Nigeria, before 2017 the most recent case of human monkeypox had been reported in 1978. By mid-November 2017, a large outbreak caused by the West African clade resulted in 146 suspected cases and 42 laboratory-confirmed cases from 14 states. Although the source is unknown, multiple sources are suspected.

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article’s inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article’s methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

Page last reviewed: January 31, 2019